curcumin and Thyroid-Neoplasms

Unprecedented community containment measures were taken following the recent outbreak of COVID-19 in Italy. The aim of the study was to explore the self-reported future compliance of citizens with such measures and its relationship with potentially impactful psychological variables.. An online survey was completed by 931 people (18-76 years) distributed across the Italian territory. In addition to demographics, five dimensions were measured: self-reported compliance with containment measures over time (today, at 7, 14, 30, 60, 90, and 180 days from now) at three hypothetical risk levels (10, 50, 90% of likelihood of contracting the COVID-19), perceived risk, generalized anxiety, intolerance of uncertainty, and relevance of several psychological needs whose satisfaction is currently precluded.. The duration of containment measures plays a crucial role in tackling the spread of the disease as people will be less compliant over time. Psychological needs of citizens impacting on the compliance should be taken into account when planning an easing of the lockdown, along with interventions for protecting vulnerable groups from mental distress.. La apendicitis aguda (AA) es la urgencia quirúrgica abdominal más frecuente. No encontramos estudios específicos que evalúen el impacto de la pandemia causada por el coronavirus 2 (SARS-Cov-2) sobre la AA y su tratamiento quirúrgico. Analizamos la influencia de esta nueva patología sobre la AA.. Estudio observacional retrospectivo en pacientes intervenidos por AA desde enero hasta abril de 2020. Fueron clasificados según el momento de la apendicectomía, antes de la declaración del estado de alarma (Pre-COVID19) y después de la declaración del estado de alarma (Post-COVID19) en España. Se evaluaron variables demográficas, duración de la sintomatología, tipo de apendicitis, tiempo quirúrgico, estancia hospitalaria y complicaciones postoperatorias.. La pandemia por SARS-Cov-2 influye en el momento de diagnóstico de la apendicitis, así como en su grado de evolución y estancia hospitalaria. La peritonitis fue lo más frecuentemente observado. Una sospecha y orientación clínica más temprana, es necesaria para evitar un manejo inadecuado de este trastorno quirúrgico común.. The primary outcome is improvement in PaO. Findings will provide timely information on the safety, efficacy, and optimal dosing of t-PA to treat moderate/severe COVID-19-induced ARDS, which can be rapidly adapted to a phase III trial (NCT04357730; FDA IND 149634).. None.. The gut barrier is crucial in cirrhosis in preventing infection-causing bacteria that normally live in the gut from accessing the liver and other organs via the bloodstream. Herein, we characterised gut inflammation by measuring different markers in stool samples from patients at different stages of cirrhosis and comparing this to healthy people. These markers, when compared with equivalent markers usually measured in blood, were found to be very different in pattern and absolute levels, suggesting that there is significant gut inflammation in cirrhosis related to different immune system pathways to that seen outside of the gut. This provides new insights into gut-specific immune disturbances that predispose to complications of cirrhosis, and emphasises that a better understanding of the gut-liver axis is necessary to develop better targeted therapies.. La surveillance de l’intervalle QT a suscité beaucoup d’intérêt durant la pandémie de la COVID-19 en raison de l’utilisation de médicaments prolongeant l’intervalle QT et les préoccupations quant à la transmission virale par les électrocardiogrammes (ECG) en série. Nous avons posé l’hypothèse que la surveillance en continu de l’intervalle QT par télémétrie était associée à une meilleure détection des épisodes de prolongation de l’intervalle QT.. Nous avons introduit la télémétrie cardiaque en continu (TCC) à l’aide d’un algorithme de surveillance automatisée de l’intervalle QT dans nos unités de COVID-19. Les mesures automatisées quotidiennes de l’intervalle QT corrigé (auto-QTc) en fonction de la fréquence cardiaque maximale ont été enregistrées. Nous avons comparé la proportion des épisodes de prolongation marquée de l’intervalle QTc (QTc long), définie par un intervalle QTc ≥ 500 ms, chez les patients montrant une suspicion de COVID-19 ou ayant la COVID-19 qui avaient été admis avant et après la mise en place de la TCC (groupe témoin. La surveillance en continu de l’intervalle QT est supérieure à la norme de soins dans la détection des épisodes de QTc long et exige peu d’ECG. La réponse clinique aux épisodes de QTc long est sous-optimale.. Exposure to a model wildfire air pollution source modifies cardiovascular responses to HC challenge, suggesting air pollution sensitizes the body to systemic triggers.. Though the majority of HIV-infected adults who were on HAART had shown viral suppression, the rate of suppression was sub-optimal according to the UNAIDS 90-90-90 target to help end the AIDS pandemic by 2020. Nonetheless, the rate of immunological recovery in the study cohort was low. Hence, early initiation of HAART should be strengthened to achieve good virological suppression and immunological recovery.. Dust in Egyptian laying hen houses contains high concentrations of microorganisms and endotoxins, which might impair the health of birds and farmers when inhaled. Furthermore, laying hens in Egypt seem to be a reservoir for ESBL-producing Enterobacteriaceae. Thus, farmers are at risk of exposure to ESBL-producing bacteria, and colonized hens might transmit these bacteria into the food chain.. The lack of significant differences in the absolute changes and relative ratios of injury and repair biomarkers by contrast-associated AKI status suggests that the majority of mild contrast-associated AKI cases may be driven by hemodynamic changes at the kidney.. Most comparisons for different outcomes are based on very few studies, mostly low-powered, with an overall low CoE. Thus, the available evidence is considered insufficient to either support or refute CH effectiveness or to recommend one ICM over another. Therefore, further well-designed, larger RCTs are required.. PROSPERO database Identifier: CRD42016041953.. Untouched root canal at cross-section perimeter, the Hero 642 system showed 41.44% ± 5.62% and Reciproc R40 58.67% ± 12.39% without contact with instruments. Regarding the untouched area, Hero 642 system showed 22.78% ± 6.42% and Reciproc R40 34.35% ± 8.52%. Neither instrument achieved complete cross-sectional root canal debridement. Hero 642 system rotary taper 0.02 instruments achieved significant greater wall contact perimeter and area compared to reciprocate the Reciproc R40 taper 0.06 instrument.. Hero 642 achieved higher wall contact perimeter and area but, regardless of instrument size and taper, vital pulp during. The functional properties of the main mechanisms involved in the control of muscle Ca. This study showed that the anti-inflammatory effect of the iron-responsive product DHA in arthritis can be monitored by an iron-like radioactive tracer (. Attenuated vascular reactivity during pregnancy suggests that the systemic vasodilatory state partially depletes nitric oxide bioavailability. Preliminary data support the potential for MRI to identify vascular dysfunction in vivo that underlies PE. Level of Evidence 2 Technical Efficacy Stage 1 J. MAGN. RESON. IMAGING 2021;53:447-455.. La evaluación de riesgo es importante para predecir los resultados postoperatorios en pacientes con cáncer gastroesofágico. Este estudio de cohortes tuvo como objetivo evaluar los cambios en la composición corporal durante la quimioterapia neoadyuvante e investigar su asociación con complicaciones postoperatorias. MÉTODOS: Los pacientes consecutivos con cáncer gastroesofágico sometidos a quimioterapia neoadyuvante y cirugía con intención curativa entre 2016 y 2019, identificados a partir de una base de datos específica, se incluyeron en el estudio. Se utilizaron las imágenes de tomografía computarizada, antes y después de la quimioterapia neoadyuvante, para evaluar el índice de masa muscular esquelética, la sarcopenia y el índice de grasa visceral y subcutánea.. In this in vitro premature infant lung model, HF oscillation of BCPAP was associated with improved CO. Our results showed that HPC significantly promotes neurogenesis after MCAO and ameliorates neuronal injury.. Inflammatory markers are highly related to signs of systemic hypoperfusion in CS. Moreover, high PCT and IL-6 levels are associated with poor prognosis.. These findings indicate that Tetrapleura tetraptera fruit has a protective potential against stroke through modulation of redox and electrolyte imbalances, and attenuation of neurotransmitter dysregulation and other neurochemical dysfunctions. Tetrapleura tetraptera fruit could be a promising source for the discovery of bioactives for stroke therapy.

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Thyroid cancer is the most frequent endocrine malignancy, with more than 500,000 cases per year worldwide. Differentiated thyroid cancers are the most common forms with best prognosis, while poorly/undifferentiated ones are rare (2% of all thyroid cancer), aggressive, frequently metastasize and have a worse prognosis. For aggressive, metastatic and advanced thyroid cancer novel antitumor molecules are urgently needed and phytochemical products can be a rational and extensive source, since secondary plant metabolites can guarantee the necessary biochemical variability for therapeutic purpose. Among bioactive molecules that present biological activity on thyroid cancer, resveratrol, curcumin, isoflavones, glucosinolates are the most common and used in experimental model. Most of them have been studied both in vitro and in vivo on this cancer, but rarely in clinical trial. This review summarizes phytochemicals, phytotherapeutics and plant derived compounds used in thyroid cancer.

Topics: Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Clinical Trials as Topic; Curcumin; Humans; Isoflavones; Molecular Structure; Phytochemicals; Quercetin; Resveratrol; Thyroid Neoplasms

Thyroid cancers developed from the tissues of the thyroid gland are classified into papillary (PTC), follicular (FTC), medullary (MTC), and anaplastic thyroid cancer (ATC). Although thyroid cancers have been generally known as mild forms of cancer, undifferentiated MTC and ATC have a more unfavorable prognosis than differentiated PTC and FTC because they are more aggressive and early metastatic. A variety of therapies such as surgery, radiotherapy, and chemotherapy have been currently used to treat thyroid cancer, but they still have limitations including drug resistance or unfavorable side effects. Phytochemicals are plant-derived chemicals having various physiological activities that are expected to be effective in cancer treatment. In this review, anticancer efficacy of phytochemicals, such as resveratrol, genistein, curcumin, and other substances in each type of thyroid cancer was introduced with their chemopreventive mechanisms. English articles related with thyroid cancer and anti-thyroid cancer of phytochemicals were searched from PubMed and Google Scholar. This article mainly focused on in vitro or animal studies on phytochemicals with anti-thyroid cancer activity. These various phytochemicals have been shown to induce apoptosis in all types of thyroid cancer cells, inhibit cell proliferation and invasion, and to be helpful in enhancing the effect of radioiodine therapy that is a typical therapy to thyroid cancer. These results suggest that thyroid cancer can be more effectively treated by the combinations of phytochemicals and the existing therapies or substances.

Topics: Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Cell Line, Tumor; Cell Proliferation; Curcumin; Disease Models, Animal; Humans; Isoflavones; Phytochemicals; Resveratrol; Thyroid Carcinoma, Anaplastic; Thyroid Gland; Thyroid Neoplasms

Unprecedented community containment measures were taken following the recent outbreak of COVID-19 in Italy. The aim of the study was to explore the self-reported future compliance of citizens with such measures and its relationship with potentially impactful psychological variables.. An online survey was completed by 931 people (18-76 years) distributed across the Italian territory. In addition to demographics, five dimensions were measured: self-reported compliance with containment measures over time (today, at 7, 14, 30, 60, 90, and 180 days from now) at three hypothetical risk levels (10, 50, 90% of likelihood of contracting the COVID-19), perceived risk, generalized anxiety, intolerance of uncertainty, and relevance of several psychological needs whose satisfaction is currently precluded.. The duration of containment measures plays a crucial role in tackling the spread of the disease as people will be less compliant over time. Psychological needs of citizens impacting on the compliance should be taken into account when planning an easing of the lockdown, along with interventions for protecting vulnerable groups from mental distress.. La apendicitis aguda (AA) es la urgencia quirúrgica abdominal más frecuente. No encontramos estudios específicos que evalúen el impacto de la pandemia causada por el coronavirus 2 (SARS-Cov-2) sobre la AA y su tratamiento quirúrgico. Analizamos la influencia de esta nueva patología sobre la AA.. Estudio observacional retrospectivo en pacientes intervenidos por AA desde enero hasta abril de 2020. Fueron clasificados según el momento de la apendicectomía, antes de la declaración del estado de alarma (Pre-COVID19) y después de la declaración del estado de alarma (Post-COVID19) en España. Se evaluaron variables demográficas, duración de la sintomatología, tipo de apendicitis, tiempo quirúrgico, estancia hospitalaria y complicaciones postoperatorias.. La pandemia por SARS-Cov-2 influye en el momento de diagnóstico de la apendicitis, así como en su grado de evolución y estancia hospitalaria. La peritonitis fue lo más frecuentemente observado. Una sospecha y orientación clínica más temprana, es necesaria para evitar un manejo inadecuado de este trastorno quirúrgico común.. The primary outcome is improvement in PaO. Findings will provide timely information on the safety, efficacy, and optimal dosing of t-PA to treat moderate/severe COVID-19-induced ARDS, which can be rapidly adapted to a phase III trial (NCT04357730; FDA IND 149634).. None.. The gut barrier is crucial in cirrhosis in preventing infection-causing bacteria that normally live in the gut from accessing the liver and other organs via the bloodstream. Herein, we characterised gut inflammation by measuring different markers in stool samples from patients at different stages of cirrhosis and comparing this to healthy people. These markers, when compared with equivalent markers usually measured in blood, were found to be very different in pattern and absolute levels, suggesting that there is significant gut inflammation in cirrhosis related to different immune system pathways to that seen outside of the gut. This provides new insights into gut-specific immune disturbances that predispose to complications of cirrhosis, and emphasises that a better understanding of the gut-liver axis is necessary to develop better targeted therapies.. La surveillance de l’intervalle QT a suscité beaucoup d’intérêt durant la pandémie de la COVID-19 en raison de l’utilisation de médicaments prolongeant l’intervalle QT et les préoccupations quant à la transmission virale par les électrocardiogrammes (ECG) en série. Nous avons posé l’hypothèse que la surveillance en continu de l’intervalle QT par télémétrie était associée à une meilleure détection des épisodes de prolongation de l’intervalle QT.. Nous avons introduit la télémétrie cardiaque en continu (TCC) à l’aide d’un algorithme de surveillance automatisée de l’intervalle QT dans nos unités de COVID-19. Les mesures automatisées quotidiennes de l’intervalle QT corrigé (auto-QTc) en fonction de la fréquence cardiaque maximale ont été enregistrées. Nous avons comparé la proportion des épisodes de prolongation marquée de l’intervalle QTc (QTc long), définie par un intervalle QTc ≥ 500 ms, chez les patients montrant une suspicion de COVID-19 ou ayant la COVID-19 qui avaient été admis avant et après la mise en place de la TCC (groupe témoin. La surveillance en continu de l’intervalle QT est supérieure à la norme de soins dans la détection des épisodes de QTc long et exige peu d’ECG. La réponse clinique aux épisodes de QTc long est sous-optimale.. Exposure to a model wildfire air pollution source modifies cardiovascular responses to HC challenge, suggesting air pollution sensitizes the body to systemic triggers.. Though the majority of HIV-infected adults who were on HAART had shown viral suppression, the rate of suppression was sub-optimal according to the UNAIDS 90-90-90 target to help end the AIDS pandemic by 2020. Nonetheless, the rate of immunological recovery in the study cohort was low. Hence, early initiation of HAART should be strengthened to achieve good virological suppression and immunological recovery.. Dust in Egyptian laying hen houses contains high concentrations of microorganisms and endotoxins, which might impair the health of birds and farmers when inhaled. Furthermore, laying hens in Egypt seem to be a reservoir for ESBL-producing Enterobacteriaceae. Thus, farmers are at risk of exposure to ESBL-producing bacteria, and colonized hens might transmit these bacteria into the food chain.. The lack of significant differences in the absolute changes and relative ratios of injury and repair biomarkers by contrast-associated AKI status suggests that the majority of mild contrast-associated AKI cases may be driven by hemodynamic changes at the kidney.. Most comparisons for different outcomes are based on very few studies, mostly low-powered, with an overall low CoE. Thus, the available evidence is considered insufficient to either support or refute CH effectiveness or to recommend one ICM over another. Therefore, further well-designed, larger RCTs are required.. PROSPERO database Identifier: CRD42016041953.. Untouched root canal at cross-section perimeter, the Hero 642 system showed 41.44% ± 5.62% and Reciproc R40 58.67% ± 12.39% without contact with instruments. Regarding the untouched area, Hero 642 system showed 22.78% ± 6.42% and Reciproc R40 34.35% ± 8.52%. Neither instrument achieved complete cross-sectional root canal debridement. Hero 642 system rotary taper 0.02 instruments achieved significant greater wall contact perimeter and area compared to reciprocate the Reciproc R40 taper 0.06 instrument.. Hero 642 achieved higher wall contact perimeter and area but, regardless of instrument size and taper, vital pulp during. The functional properties of the main mechanisms involved in the control of muscle Ca. This study showed that the anti-inflammatory effect of the iron-responsive product DHA in arthritis can be monitored by an iron-like radioactive tracer (. Attenuated vascular reactivity during pregnancy suggests that the systemic vasodilatory state partially depletes nitric oxide bioavailability. Preliminary data support the potential for MRI to identify vascular dysfunction in vivo that underlies PE. Level of Evidence 2 Technical Efficacy Stage 1 J. MAGN. RESON. IMAGING 2021;53:447-455.. La evaluación de riesgo es importante para predecir los resultados postoperatorios en pacientes con cáncer gastroesofágico. Este estudio de cohortes tuvo como objetivo evaluar los cambios en la composición corporal durante la quimioterapia neoadyuvante e investigar su asociación con complicaciones postoperatorias. MÉTODOS: Los pacientes consecutivos con cáncer gastroesofágico sometidos a quimioterapia neoadyuvante y cirugía con intención curativa entre 2016 y 2019, identificados a partir de una base de datos específica, se incluyeron en el estudio. Se utilizaron las imágenes de tomografía computarizada, antes y después de la quimioterapia neoadyuvante, para evaluar el índice de masa muscular esquelética, la sarcopenia y el índice de grasa visceral y subcutánea.. In this in vitro premature infant lung model, HF oscillation of BCPAP was associated with improved CO. Our results showed that HPC significantly promotes neurogenesis after MCAO and ameliorates neuronal injury.. Inflammatory markers are highly related to signs of systemic hypoperfusion in CS. Moreover, high PCT and IL-6 levels are associated with poor prognosis.. These findings indicate that Tetrapleura tetraptera fruit has a protective potential against stroke through modulation of redox and electrolyte imbalances, and attenuation of neurotransmitter dysregulation and other neurochemical dysfunctions. Tetrapleura tetraptera fruit could be a promising source for the discovery of bioactives for stroke therapy.

Topics: 3T3-L1 Cells; A Kinase Anchor Proteins; Acetates; Achilles Tendon; Acute Kidney Injury; Acute Pain; Acyclic Monoterpenes; Adenine Nucleotides; Adhesins, Escherichia coli; Adipocytes; Adipocytes, Brown; Adipogenesis; Administration, Inhalation; Administration, Oral; Adrenal Cortex Hormones; Adsorption; Adult; Aeromonas hydrophila; Africa; Aged; Aged, 80 and over; Agrobacterium tumefaciens; Air; Air Pollutants; Air Pollution; Air Pollution, Indoor; Algorithms; Alkaloids; Alkynes; Allosteric Regulation; Amines; Amino Acid Sequence; Amino Acids; Amino Acids, Branched-Chain; Aminoisobutyric Acids; Aminopyridines; Amyotrophic Lateral Sclerosis; Anaerobic Threshold; Angiography; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animal Distribution; Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Ankle Joint; Anti-Bacterial Agents; Anti-HIV Agents; Anti-Inflammatory Agents; Antibodies, Bacterial; Antifungal Agents; 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Thyroid cancer is the most common endocrine tumor. Our previous studies have demonstrated that curcumin can induce apoptosis in human papillary thyroid carcinoma BCPAP cells. However, the underlined mechanism has not been clearly elucidated. Endoplasmic reticulum (ER) is a major organelle for synthesis, maturation, and folding proteins as well as a large store for Ca. Overcoming chronically activated ER stress by triggering pro-apoptotic pathways of the unfolded protein response (UPR) is a novel strategy for cancer therapeutics. Our study aimed to uncover the ER stress pathway involved in the apoptosis caused by curcumin.. BCPAP cells were treated with different doses of curcumin (12.5-50 μM). Annexin V/PI double staining was used to determine cell apoptosis. Rhod-2/AM calcium fluorescence probe assay was performed to measure the calcium level of endoplasmic reticulum. Western blot was used to examine the expression of ER stress marker C/EBP homologous protein 10 (CHOP) and glucose-regulated protein 78 (GRP78). X-box binding protein1 (XBP-1) spliced form was examined by reverse transcriptase-polymerase chain reaction (RT-PCR).. Curcumin significantly inhibited anchorage-independent cell growth and induced apoptosis in BCPAP cells. Curcumin induced ER stress and UPR responses in a dose- and time-dependent manner, and the chemical chaperone 4-phenylbutyrate (4-PBA) partially reversed the antigrowth activity of curcumin. Moreover, curcumin significantly increased inositol-requiring enzyme 1α (IRE1α) phosphorylation and XBP-1 mRNA splicing to induce a subsets of ER chaperones. Increased cleavage of activating transcription factor 6 (ATF6), which enhances expression of its downstream target CHOP was also observed. Furthermore, curcumin induced intracellular Ca influx through inhibition of the sarco-endoplasmic reticulum ATPase 2A (SERCA2) pump. The increased cytosolic Ca then bound to calmodulin to activate calcium/calmodulin-dependent protein kinase II (CaMKII) signaling, leading to mitochondrial apoptosis pathway activation. Ca chelator BAPTA partially reversed curcumin-induced ER stress and growth suppression, confirming the possible involvement of calcium homeostasis disruption in this response.. Curcumin inhibits thyroid cancer cell growth, at least partially, through ER stress-associated apoptosis. Our observations provoked that ER stress activation may be a promising therapeutic target for thyroid cancer treatment.(Figure is included in full-text article.).

Topics: Apoptosis; Blotting, Western; Calcium; Carcinoma, Papillary; Cell Line, Tumor; Cell Survival; Colony-Forming Units Assay; Curcumin; Endoplasmic Reticulum; Endoplasmic Reticulum Chaperone BiP; Endoplasmic Reticulum Stress; Homeostasis; Humans; Reverse Transcriptase Polymerase Chain Reaction; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Signal Transduction; Thyroid Cancer, Papillary; Thyroid Neoplasms; Transcription Factor CHOP

Follicular thyroid cancer (FTC) is a highly aggressive type of endocrine malignancy. It is necessary to investigate the mechanisms of tumorigenesis and therapeutic pathways in patients with FTC. Haem oxygenase-1 (HO-1) can regulate oxidative stress and the occurrence of tumors and diseases. In this study, we discovered that HO-1 was abnormally overexpressed in FTC compared with adjacent tissues. However, the HO-1 overexpression was demonstrated to decrease cell viability and to potentially activate the ferroptosis signalling pathway. Ferroptosis is a newly identified form of oxidative cell death and is currently being targeted as a new cancer treatment. Tumorigenesis is significantly inhibited by curcumin. The present study shows that curcumin inhibits the growth of FTC by increasing the HO-1 expression, further activating the ferroptosis pathway. This study demonstrates that the HO-1-ferroptosis signalling pathway might play an important role in FTC tumorigenesis, and that curcumin inhibits the growth of FTC cells by affecting this pathway.

Topics: Adenocarcinoma, Follicular; Carcinogenesis; Curcumin; Ferroptosis; Heme Oxygenase-1; Humans; Thyroid Neoplasms

Anaplastic thyroid carcinoma (ATC) is the rarest type of thyroid cancer, but is the common cause of death from these tumors. The aggressive behavior of ATC makes it resistant to the conventional therapeutic approaches. Thus, the present study was designed to evaluate the anti-ATC efficacy of the piperidone analogue of curcumin (PAC). We have shown that PAC induces apoptosis in thyroid cancer cells in a time-dependent fashion through the mitochondrial pathway. Immunoblotting analysis revealed that PAC suppressed the epithelial-to-mesenchymal transition (EMT) process in ATC cells by upregulating the epithelial marker E-cadherin and reducing the level of the mesenchymal markers N-cadherin, Snail, and Twist1. This anti-EMT effect was confirmed by showing PAC-dependent inhibition of the proliferation and migration abilities of ATC cells. Furthermore, PAC inhibited the AKT/mTOR pathway in ATC cells. Indeed, PAC downregulated mTOR and its downstream effectors p70S6K and 4E-BP1 more efficiently than the well-known mTOR inhibitor rapamycin. In addition to the promising in vitro anticancer efficacy, PAC significantly suppressed the growth of humanized thyroid tumor xenografts in mice. Together, these findings indicate that PAC could be considered as promising therapeutic agent for anaplastic thyroid carcinomas.

Topics: Animals; Apoptosis; Cell Line, Tumor; Cell Proliferation; Curcumin; Humans; Mice; Piperidones; Thyroid Carcinoma, Anaplastic; Thyroid Neoplasms; TOR Serine-Threonine Kinases

Thyroid cancer is one of the most common endocrine malignancies. Differentiated thyroid cancer (DTC) treatment is based on the ability of thyroid follicular cells to accumulate radioactive iodide (RAI). DTC generally has a good prognosis. However, tumor dedifferentiation or defect in certain cell death mechanism occurs in a subset of DTC patients, leading to RAI resistance. Therefore, developing novel therapeutic approaches that enhance RAI sensitivity are still warranted. We found that curcumin, an active ingredient in turmeric with anti-cancer properties, rapidly accumulated in the mitochondria of thyroid cancer cells but not normal epithelial cells. Curcumin treatment triggered mitochondrial membrane depolarization, engulfment of mitochondria within autophagosomes and a robust decrease in mitochondrial mass and proteins, indicating that curcumin selectively induced mitophagy in thyroid cancer cells. In addition, curcumin-induced mitophagic cell death and its synergistic cytotoxic effect with radioiodine could be attenuated by autophagy inhibitor, 3-methyladenine (3-MA). Interestingly, the mechanism of mitophagy-inducing potential of curcumin was its unique mitochondria-targeting property, which induced a burst of SDH activity and excessive ROS production. Our data suggest that curcumin induces mitochondrial dysfunction and triggers lethal mitophagy, which synergizes with radioiodine to kill thyroid cancer cells.

Topics: Cell Line, Tumor; Curcumin; Humans; Iodine Radioisotopes; Mitochondria; Mitophagy; Succinate Dehydrogenase; Thyroid Cancer, Papillary; Thyroid Neoplasms

Curcumin, a polyphenolic compound, is a well-known anticancer agent, although its poor bioavailability remains a big concern. Recent studies suggest that autophagy-targeted therapy may be a useful adjunct treatment for patients with thyroid cancer. Curcumin acts as an autophagy inducer on many cancer cells. However, little is known about the exact role of curcumin on thyroid cancer cells. In the present study, curcumin significantly inhibited the growth of thyroid cancer cells. Autophagy was markedly induced by curcumin treatment as evidenced by an increase in LC3-II conversion, beclin-1 accumulation, p62 degradation as well as the increased formation of acidic vesicular organelles (AVOs). 3-MA, an autophagy inhibitor, partially rescued thyroid cancer cells from curcumin-induced cell death. Additionally, curcumin was found to exert selective cytotoxicity on thyroid cancer cells but not normal epithelial cells and acted as an autophagy inducer through activation of MAPK while inhibition of mTOR pathways. Hyperactivation of the AKT/mTOR axis was observed in the majority of PTC samples we tested, and thyroid cancer cell lines along with cancer tissue specimens sustained a low basal autophagic activity. Taken together, our results provide new evidence that inducing autophagic cell death may serve as a potential anti-cancer strategy to handle thyroid cancer.

Topics: Adenine; Antineoplastic Agents; Autophagic Cell Death; Cell Line; Cell Line, Tumor; Cell Survival; Cells, Cultured; Curcumin; Humans; Proto-Oncogene Proteins c-akt; Signal Transduction; Thyroid Neoplasms; TOR Serine-Threonine Kinases

Papillary thyroid cancer (PTC) is a type of epithelial-derived differentiated TC that reportedly accounts for a majority of TCs. Curcumin, a polyphenolic compound and a member of the Zingiberaceae (ginger) family derived from turmeric plants, can exhibit anticancer effects. Herein, we aimed to investigate the effect of curcumin on PTC and elucidate underlying mechanisms. Accordingly, PTC B-CPAP cells were treated with curcumin, in combination with/without long noncoding RNA LINC00691 inhibition, to determine the effect of curcumin and its relationship with LINC00691 in PTC cells. We observed that curcumin treatment decreased B-CPAP cell proliferation and promoted apoptosis. Curcumin inhibited LINC00691 expression in B-CPAP cells. Curcumin administration or si-LINC00691 transfection alone promoted ATP levels, inhibited glucose uptake and lactic acid levels, and inhibited lactate dehydrogenase A and hexokinase 2 protein expression in B-CPAP cells, which were further enhanced by combination treatment. Moreover, curcumin administration or si-LINC00691 transfection alone inhibited p-Akt activity, further suppressed by combination treatment. Akt inhibition promoted apoptosis and suppressed the Warburg effect in B-CPAP cells. In conclusion, our findings indicate that curcumin promotes apoptosis and suppresses proliferation and the Warburg effect by inhibiting LINC00691 in B-CPAP cells. The precise molecular mechanism might be mediated through the Akt signaling pathway, providing a theoretical basis for the treatment of PTC with curcumin.

Topics: Apoptosis; Cell Line, Tumor; Cell Movement; Cell Proliferation; Curcumin; Gene Expression Regulation, Neoplastic; Humans; RNA, Long Noncoding; Thyroid Cancer, Papillary; Thyroid Neoplasms

Radioactive iodine (RAI) is commonly used to treat differentiated thyroid cancer (DTC). A major challenge is the dedifferentiation of DTC with the loss of radioiodine uptake. Patients with distant metastases have persistent or recurrent disease and develop resistance to RAI therapy due to tumor dedifferentiation. Hence, tumor redifferentiation to restore sensitivity to RAI therapy is considered a promising strategy to overcome RAI resistance. In the present study, curcumin, a natural polyphenolic compound, was found to re-induce cell differentiation and increase the expression of thyroid-specific transcription factors, TTF-1, TTF-2 and transcriptional factor paired box 8 (PAX8), and iodide-metabolizing proteins, including thyroid stimulating hormone receptor (TSHR), thyroid peroxidase (TPO) and sodium iodide symporter (NIS) in dedifferentiated thyroid cancer cell lines, BCPAP and KTC-1. Importantly, curcumin enhanced NIS glycosylation and its membrane trafficking, resulting in a significant improvement of radioiodine uptake

Topics: Cell Line, Tumor; Cell Membrane; Cell Survival; Curcumin; Cytoplasm; Gene Expression Regulation, Neoplastic; Humans; Iodine Radioisotopes; Phosphatidylinositol 3-Kinases; Protein Transport; Proto-Oncogene Proteins c-akt; Symporters; Thyroid Neoplasms; Transcriptome

Curcumin has been recognized as an effective anticancer agent. However, due to its hydrophobic property, the cell absorption is not satisfied. Herein, the curcumin nanoparticles were prepared in the presence of polyethylene glycol 6000 (PEG6000) to reduce its elimination by immune system. For first time, not only the curcumin was encapsulated within the niosome nanoparticles modified by PEG, there are no reports related to the anticancer property of curcumin against thyroid cancers. The nanoparticles was developed and its anticancer was studied on sw-1736 cancer cell line. The nanoparticles were examined by scanning electron microscopy (SEM) and dynamic light scattering (DLS). Also, the release profile of curcumin, the IC50 concentration, the radical amount and the gene expression were evaluated. The optimized nanoparticles showed a diameter of 212 ± 31 nm by SEM and the encapsulation efficiency and loading capacity of 76% and 16.8% respectively. DLS confirmed the polydispersity index (PDI) of 0.596 and the release model was shown a sustained release with the delivery of 68% curcumin after 6 days. Also, the nanoparticles indicated the higher storage stability at 4 °C. After the cell treatment, the apoptotic bodies were appeared and IC50 was obtained as 0.159 mM. Moreover, the generated radicals by the treated cells was 86% after 72 h and the gene pattern indicated the bax/bcl2 ratio of 6.83 confirming the apoptosis effect of the nanoparticles. The results approved the nanoparticles could be suggested as an anticancer drug candidate for thyroid cancers. The encapsulated curcumin within the niosome nanoparticles modified with PEG, could be released and up-taken by the thyroid cancer cell line due to the same hydrophobic property of cell membrane and the niosome particles. The reaction between curcumin and cellular components generates radicals and activates the apoptotic pathway. The corresponding reaction finally makes cell death.

Topics: Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Cells, Cultured; Curcumin; Drug Carriers; Drug Compounding; Drug Liberation; Drug Stability; Drug Synergism; Gene Expression Regulation, Neoplastic; Humans; Liposomes; Nanoparticles; Particle Size; Polyethylene Glycols; Thyroid Neoplasms

The constitutive activation of Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) signal transduction is well elucidated in STAT3-mediated oncogenesis related to thyroid cancer and is considered to be a plausible therapeutic target. Hence, we investigated whether curcumin, a natural compound, can target the JAK/STAT3 signaling pathway to induce cytotoxic effects in papillary thyroid cancer (PTC) cell lines (BCPAP and TPC-1) and derived thyroid cancer stem-like cells (thyrospheres). Curcumin suppressed PTC cell survival in a dose-dependent manner via the induction of caspase-mediated apoptosis and caused the attenuation of constitutively active STAT3 (the dephosphorylation of Tyr705-STAT3) without affecting STAT3. Gene silencing with STAT3-specific siRNA showed the modulation of genes associated with cell growth and proliferation. The cotreatment of PTC cell lines with curcumin and cisplatin synergistically potentiated cytotoxic effects via the suppression of JAK/STAT3 activity along with the inhibition of antiapoptotic genes and the induction of proapoptotic genes, and it also suppressed the migration of PTC cells by downregulating matrix metalloproteinases and the inhibition of colony formation. Finally, thyrospheres treated with curcumin and cisplatin showed suppressed STAT3 phosphorylation, a reduced formation of thyrospheres, and the downregulated expression of stemness markers, in addition to apoptosis. The current study's findings suggest that curcumin synergistically enhances the anticancer activity of cisplatin in PTC cells as well as in cancer stem-like cells by targeting STAT3, which suggests that curcumin combined with chemotherapeutic agents may provide better therapeutic outcomes.

Topics: Apoptosis; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cell Survival; Cisplatin; Curcumin; Drug Synergism; Humans; Interleukin-6; Janus Kinases; Neoplastic Stem Cells; Reactive Oxygen Species; Signal Transduction; STAT3 Transcription Factor; Thyroid Cancer, Papillary; Thyroid Neoplasms; Up-Regulation

Anaplastic Thyroid Cancer (ATC) is one of the most lethal and aggressive human malignancies. Studies have shown that Cancer Stem-Cell (CSC) phenotype is mainly responsible for ATC aggressiveness. Cytostatic compounds are mostly ineffective because of multidrug resistance mechanisms driven by the CSC phenotype. Taxanes have limited efficacy. Recently, CSC inhibition using plant-derived, less toxic compounds, which have anti-cancer efficacy, has become a novel treatment modality. The aim of the study was to evaluate the anti-cancer activity of two natural compounds (curcumin and deguelin) on ATC cells and their CSC properties. In addition, the efficacies of these compounds were compared with that of docetaxel.. Besides control, five treatment groups were formed. ATC cells (CAL-62) were treated with curcumin, deguelin, docetaxel, and their combinations (curcumin+docetaxel, deguelin+docetaxel) at previously determined IC50 doses. Stemness was analyzed by quantitative estimation of sphere formation in matrigel, expression of several cell surface markers (CD133, CD90, Nanog, and OCT3/4) using flow cytometry, and quantification of the hypoxic status [Oxidative Stress Index (OSI) and Superoxide Dismutase (SOD) activity]. The anti-cancer efficacies of these compounds and their combinations were evaluated by determining the alterations in the cell cycle, apoptosis, and tumoral cell migration.. Both the natural compounds (particularly curcumin) significantly suppressed the spheroid formation and cellular motility in matrigel as well as suppressed the accumulation of cells in the G0/1 phase, in which the maximum CSC activity is observed. The compounds did not suppress the expression of CSC markers, but twothirds of the cells expressed CD90. Deguelin was found to be particularly effective in inducing apoptosis similar to docetaxel at IC50 concentrations. Curcumin reduced the OSI and deguelin enhanced the SOD activity, even in docetaxel pre-treated cells.. A large proportion of anaplastic tumors might consist of heterogeneous CSC population. Curcumin and deguelin have anti-cancer and several anti-stem cell activities against ATC cells. These natural compounds are capable of altering the aggressive behavior of ATC cells through the inhibition of the CSC phenotype. As a novel therapeutic target, CD90 should be investigated in other ATC cell lines and in vivo models.

Topics: AC133 Antigen; Apoptosis; Cell Cycle; Cell Line, Tumor; Curcumin; Docetaxel; Drug Therapy, Combination; Humans; Nanog Homeobox Protein; Neoplastic Stem Cells; Octamer Transcription Factors; Oxidative Stress; Phenotype; Rotenone; Superoxide Dismutase; Thy-1 Antigens; Thyroid Carcinoma, Anaplastic; Thyroid Neoplasms

The anaplastic thyroid carcinoma (ATC) is the most aggressive thyroid cancer with a high mortality rate. Since nutraceuticals may exert beneficial effects on tumor biology, here, effects of four of these compounds [resveratrol, genistein, curcumin and epigallocatechin-3-gallate (EGCG)] on ATC cell lines were investigated.. Two ATC-derived cell lines were used: SW1736 and 8505C. Cell viability and in vitro aggressiveness was tested by MTT and soft agar assays. Apoptosis was investigated by Western Blot, using an anti-cleaved-PARP antibody. mRNA and miRNA levels were quantified by real-time PCR.. All tested nutraceuticals caused in both cell lines decrease of cell viability and increase of apoptosis. In contrast, only curcumin reduced in vitro aggressiveness in both SW1736 and 8505C cell lines, while genistein and EGCG determined a reduction of colony formation only in 8505C cells. Effects on genes related to the thyroid-differentiated phenotype were also tested: resveratrol and genistein administration determined the increment of almost all tested mRNAs in both cell lines. Instead curcumin and EGCG treatments had opposite effects in the two cell lines, causing the increment of almost all the mRNAs in 8505C cells and their reduction in SW1736. Finally, effects of nutraceuticals on levels of several miRNAs, known as important in thyroid cancer progression (hsa-miR-221, hsa-miR-222, hsa-miR-21, hsa-miR-146b, hsa-miR-204), were tested. Curcumin induced a strong and significant reduction of all miR analyzed, except for has-miR-204, in both cell lines.. Altogether, our results clearly indicate the anti-cancer proprieties of curcumin, suggesting the promising use of this nutraceutical in ATC treatment. Resveratrol, genistein and EGCG have heterogeneous effects on molecular features of ATC cells.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Catechin; Cell Differentiation; Cell Growth Processes; Cell Line, Tumor; Curcumin; Dietary Supplements; Genistein; Humans; MicroRNAs; Resveratrol; Stilbenes; Thyroid Carcinoma, Anaplastic; Thyroid Neoplasms

The thyroid gland is one of the largest endocrine glands in the body. The vast majority of TCs (> 90%) originate from follicular cells and are defined as differentiated thyroid cancers (DTC) and the two histological subtypes are the papillary TC with its variants and the follicular TC. Curcumin possesses a wide variety of biological functions, and thanks to its properties, it has gained considerable attention due to its profound medicinal values (Prasad, Gupta, Tyagi, and Aggarwal, Biotechnol Adv 32:1053-1064, 2014). We have undertaken the present work in order to define the possible role of curcumin in modulating the genetic expression of cell markers and to understand the effectiveness of this nutraceutical in modulating the regression of cancer phenotype.. As a template we used the TPC-1 cells treated with the different extracts of turmeric, and examined the levels of expression of different markers (proliferative, inflammatory, antioxidant, apoptotic).. Treatment with the three different curcumin extracts displays anti-inflammatory, antioxidant properties and it is able to influence cell cycle with slightly different effects upon the extracts. Furthermore curcumin is able to influence cell metabolic activity vitality.. In conclusion curcumin has the potential to be developed as a safe therapeutic but further studies are needed to verify its antitumor ability in vivo.

Topics: Apoptosis; Carcinoma, Papillary; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Curcuma; Curcumin; Humans; Thyroid Cancer, Papillary; Thyroid Neoplasms

The therapy of unresectable advanced thyroid carcinomas shows unfavorable outcome. Constitutive nuclear factor-κB (NF-κB) activation in thyroid carcinomas frequently contributes to therapeutic resistance; the radioiodine therapy often fails due to the loss of differentiated functions in advanced thyroid carcinomas. Curcumin is known for its anticancer properties in a series of cancers, but only few studies have focused on thyroid cancer. Our aim was to evaluate curcumin's molecular mechanisms and to estimate if curcumin could be a new therapeutic option in advanced thyroid cancer.. Human thyroid cancer cell lines TPC-1 (papillary), FTC-133 (follicular), and BHT-101 (anaplastic) were treated with curcumin. Using real-time PCR analysis, we investigated microRNA (miRNA) and mRNA expression levels. Cell cycle, Annexin V/PI staining, and caspase-3 activity analysis were performed to detect apoptosis. NF-κB p65 activity and cell proliferation were analyzed using appropriate ELISA-based colorimetric assay kits.. Treatment with 50 μM curcumin significantly increased the mRNA expression of the differentiation genes thyroglobulin (TG) and sodium iodide symporter (NIS) in all three cell lines and induced inhibition of cell proliferation, apoptosis, and decrease of NF-κB p65 activity. The miRNA expression analyses showed a significant deregulation of miRNA-200c, -21, -let7c, -26a, and -125b, known to regulate cell differentiation and tumor progression. Curcumin arrested cell growth at the G2/M phase.. Curcumin increases the expression of redifferentiation markers and induces G2/M arrest, apoptosis, and downregulation of NF-κB activity in thyroid carcinoma cells. Thus, curcumin appears to be a promising agent to overcome resistance to the conventional cancer therapy.

Topics: Antineoplastic Agents; Apoptosis; Blotting, Western; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Proliferation; Curcumin; Enzyme-Linked Immunosorbent Assay; Gene Expression Profiling; Humans; NF-kappa B; Real-Time Polymerase Chain Reaction; Thyroid Neoplasms; Transcriptome

The objective of this study was to examine the in vitro combinatorial anticancer effects of curcumin and sorafenib towards thyroid cancer cells FTC133 using a MTT cytotoxicity assay, and to test whether the mechanism involves induction of apoptosis. The present results demonstrated that curcumin at 15-25 μM dose-dependently suppressed the proliferation of FTC133. Combined treatment (curcumin (25 μM) and sorafenib (2 μM)) resulted in a reduction in cell colony formation and significantly decreased the invasion and migration of FTC133 cells compared with that treated with individual drugs. Western blot showed that the levels of p-ERK and p-Akt proteins were significantly reduced (p < 0.01) in the medicine-treated FTC133 cells. The curcumin was found to dose-dependently inhibit the apoptosis of FTC133 cells possibly via PI3K/Akt and ERK pathways. There is a synergetic antitumour effect between curcumin and sorafenib.

Topics: Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Cell Line, Tumor; Cell Movement; Curcumin; Dose-Response Relationship, Drug; Humans; MAP Kinase Signaling System; Niacinamide; Phenylurea Compounds; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Signal Transduction; Sorafenib; Thyroid Neoplasms

Previously we found that curcumin, the active constituent of dietary spice turmeric, showed potent inhibitory effects on the cell growth of thyroid cancer cells. However, the detailed anti-cancer mechanism of curcumin is still unknown. In this study, we have reported that curcumin induces significant DNA damage in human papillary thyroid carcinoma BCPAP cells in a dose-dependent manner as evidenced by the upregulated phosphorylation of H2A.X at Ser139, which was further confirmed by the long tails in the comet assay and the increase in the number of TUNEL-positive cells. Subsequently, curcumin treatment caused a significant accumulation of cells at the G2/M phase that eventually resulted in a caspase-dependent apoptosis in BCPAP cells. DNA agarose gel electrophoresis revealed that curcumin-induced DNA damage in BCPAP cells was independent of DNA conformational change. Pretreatment with reactive oxygen species (ROS) scavengers failed to block the phosphorylation of H2A.X, suggesting the non-involvement of ROS in curcumin-mediated DNA damage. Interestingly, ATM/ATR activation by curcumin induced phosphorylation of Chk2 (Thr68) followed by that of Cdc25C (Ser216) and Cdc2 (Tyr15), and Cyclin B1 accumulation. In addition, the ATM-specific inhibitor KU-55933 reversed curcumin-induced phosphorylation of H2A.X. These results collectively show that curcumin treatment induced the DNA damage response via triggering an ATM-activated Chk2-Cdc25C-Cdc2 signaling pathway. These observations provide novel mechanisms and potential targets for the better understanding of the anti-cancer mechanisms of curcumin.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Ataxia Telangiectasia Mutated Proteins; Carcinoma, Papillary; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Survival; Curcumin; DNA Breaks, Double-Stranded; Humans; Morpholines; Pyrones; Reactive Oxygen Species; Thyroid Neoplasms

Thyroid cancers usually possess a good prognosis while the risks of recurrence and metastasis turn out to be a disturbing issue. Curcumin [bis(4-hydroxy-3-methoxy-phenyl)-1,6-heptadiene-3,5-dione] is a natural polyphenolic compound mainly found in turmeric (Curcuma longa). Our previous studies have demonstrated that curcumin showed proliferation-inhibitory and apoptosis-inducing effects on K1 papillary thyroid cancer cells. However, the mechanism underlying the inhibition effects of curcumin on thyroid cancer cells remains unclear. Herein, we demonstrated that curcumin remarkably increased the expression of the epithelial marker E-cadherin and repressed the expression of the mesenchymal marker vimentin in human papillary thyroid carcinoma BCPAP cells. Curcumin also suppressed multiple metastatic steps of BCPAP cells, including cell attachment, spreading as well as migration. In addition, the transcription, secretion and activation of matrix metalloproteinases (MMPs) induced by transforming growth factor-β1 (TGF-β1) in BCPAP cells were mitigated upon curcumin treatment. Further evidence showed that curcumin decreased TGF-β1-mediated phosphorylation of Smad2 and Smad3. These results revealed that curcumin inhibited the TGF-β1-induced epithelial-mesenchymal transition (EMT) via down-regulation of Smad2/3 signaling pathways. Our findings provide new evidence that the anti-metastatic and anti-EMT activities of curcumin may contribute to the development of chemo-preventive agents for thyroid cancer treatment.

Topics: Carcinoma; Carcinoma, Papillary; Cell Line, Tumor; Cell Movement; Curcumin; Down-Regulation; Epithelial-Mesenchymal Transition; Humans; Signal Transduction; Thyroid Cancer, Papillary; Thyroid Neoplasms; Transforming Growth Factor beta; Transforming Growth Factor beta3

Curcumin, traditionally used as food and medicinal purposes, has recently been reported to have protective efficacy against hypoxia. Hypoxia is one of the important reactive factors in tumor metastasis, which is a key problem in clinical thyroid cancer therapy. In present study, we investigate the anti-metastatic effect of curcumin on the K1 papillary thyroid cancer cells as well as its potential mechanisms. The results show that curcumin effectively inhibits hypoxia-induced reactive oxygen species (ROS) upregulation and significantly decreases the mRNA and protein expression levels of hypoxia-inducible factor-1α (HIF-1α) in K1 cells. Curcumin also decreases the DNA binding ability of HIF-1α to hypoxia response element (HRE). Furthermore, curcumin enhances E-cadherin expression, inhibits metalloproteinase-9 (MMP-9) enzyme activity, and weakens K1 cells migration under hypoxic conditions. In summary, these results indicate that curcumin possesses a potent anti-metastatic effect and might be an effective tumoristatic agent for the treatment of aggressive papillary thyroid cancers.

Topics: Antineoplastic Agents; Blotting, Western; Carcinoma; Carcinoma, Papillary; Cell Hypoxia; Cell Line, Tumor; Cell Movement; Curcumin; Electrophoretic Mobility Shift Assay; Humans; Neoplasm Invasiveness; Reactive Oxygen Species; Reverse Transcriptase Polymerase Chain Reaction; Thyroid Cancer, Papillary; Thyroid Neoplasms

TP53 mutation is a common event in many cancers, including thyroid carcinoma. Defective p53 activity promotes cancer resistance to therapies and a more malignant phenotype, acquiring oncogenic functions. Rescuing the function of mutant p53 (mutp53) protein is an attractive anticancer therapeutic strategy. Zn(II)-curc is a novel small molecule that has been shown to target mutp53 protein in several cancer cells, but its effect in thyroid cancer cells remains unclear. Here, we investigated whether Zn(II)-curc could affect p53 in thyroid cancer cells with both p53 mutation (R273H) and wild-type p53. Zn(II)-curc induced mutp53H273 downregulation and reactivation of wild-type functions, such as binding to canonical target promoters and target gene transactivation. This latter effect was similar to that induced by PRIMA-1. In addition, Zn(II)-curc triggered p53 target gene expression in wild-type p53-carrying cells. In combination treatments, Zn(II)-curc enhanced the antitumor activity of chemotherapeutic drugs, in both mutant and wild-type-carrying cancer cells. Taken together, our data indicate that Zn(II)-curc promotes the reactivation of p53 in thyroid cancer cells, providing in vitro evidence for a potential therapeutic approach in thyroid cancers.

Topics: Antineoplastic Agents; Blotting, Western; Cell Line, Tumor; Cell Survival; Chromatin Immunoprecipitation; Curcumin; Humans; Mutant Proteins; Mutation; Reverse Transcriptase Polymerase Chain Reaction; Thyroid Neoplasms; Tumor Suppressor Protein p53; Zinc Compounds

The objectives of this study were to evaluate the in vitro anti-tumor (human thyroid cancer cell lines) potential of curcumin and to elucidate its molecular mechanisms. Here, we investigated the effects of curcumin on the cell viability, apoptosis, migration and invasion of human thyroid cancer cell lines FTC133. We also investigated the effects of curcumin on PI3K, p-Akt, MMP1/7, and COX-2 protein expressions using Western blot. Results showed that curcumin inhibited growth, cell migration and invasion in FTC133, and promoted its apoptosis. Western blot assay data demonstrated that curcumin inhibited phosphorylation of PI3K and Akt signaling pathways and subsequently attenuated MMP1/7 and COX-2 protein expressions in FTC133. In conclusion, curcumin suppresses FTC133 cell invasion and migration by inhibiting PI3K and Akt signaling pathways. Therefore, curcumin produces anti-metastatic activity in FTC133 cells.

Topics: Antineoplastic Agents; Cell Line, Tumor; Cell Movement; Curcumin; Cyclooxygenase 2; Down-Regulation; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Humans; Matrix Metalloproteinase 1; Matrix Metalloproteinase 7; Neoplasm Invasiveness; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Signal Transduction; Thyroid Neoplasms

Curcumin, the active constituent of dietary spice turmeric, possesses a strong potential for cancer prevention and treatment. However, there is no study to address the effects of curcumin on invasion and metastasis of thyroid cancers. Thyroid cancer is the most common malignancy of endocrine organs, and its incidence rates have steadily increased over recent decades. Although most indolent tumours can be effectively managed, metastatic tumours at distant secondary sites behave aggressively and currently there is no effective form of treatment. Here, for the first time it has been reported that curcumin inhibit multiple metastasis steps of K1 papillary thyroid cancer cells. Curcumin dose-dependently suppressed viability of K1 cells as well as its cell attachment, spreading, migration and invasion abilities. Moreover, curcumin could also down-regulate the expression and activity of matrix metalloproteinase-9 (MMP-9). The findings showed that curcumin might be an effective tumouristatic agent for the treatment of aggressive papillary thyroid carcinomas.

Topics: Carcinoma; Carcinoma, Papillary; Cell Line, Tumor; Cell Movement; Curcumin; Down-Regulation; Gene Expression Regulation, Neoplastic; Humans; Matrix Metalloproteinase 9; Neoplasm Invasiveness; Neoplasm Metastasis; Thyroid Cancer, Papillary; Thyroid Neoplasms

Recently, many studies on health benefits associated with curcumin have been reported. In this study, the effects of curcumin on apoptosis of papillary thyroid cancer cell line K1 and its potential mechanisms were investigated. Curcumin was found to significantly inhibit cell viability and promoted cell apoptosis in a dose-dependent manner. Moreover, curcumin-induced cell apoptosis was characterized with a rapid stimulation of reactive oxygen species (ROS) production. Furthermore, curcumin-induced ROS generation led to the loss of mitochondrial membrane potential (MMP) and the disturbance of intracellular Ca(2+) concentration. A decrease in expression of Bcl-2 and the cleavage of poly ADP-ribose polymerase (PARP) were observed after exposure to curcumin. Results of this study may elucidate the curcumin-induced apoptosis effects on K1 cells. Thus, our results indicate a role of curcumin as health-promoting food ingredient, as well as a potential chemotherapeutic agent which is able to fight against papillary thyroid cancer.

Topics: Antineoplastic Agents; Apoptosis; Carcinoma; Carcinoma, Papillary; Curcumin; Humans; Membrane Potential, Mitochondrial; Reactive Oxygen Species; Thyroid Cancer, Papillary; Thyroid Neoplasms