curcumin and Nasopharyngeal-Neoplasms

Nasopharyngeal Cancer (NPC) is a rare type of head and neck cancer that is mainly treated by radiotherapy, but sometimes it is radioresistant. Curcumin is a polyphenolic natural product with established anticancer effects in various human cancers. Recent studies have shown that curcumin has therapeutic and radiosensitizing effects on NPC cells. In fact, it has been found that curcumin can sensitize NPC cells to radiation through different mechanisms, including modulation of ROS generation, Jab1/CSN5 and non-coding RNAs. As curcumin is safe and lacks systemic toxic effects in humans, it may be considered as a potential candidate to enhance the therapeutic effects of radiation and potentiate the efficacy of chemotherapy in the context of combination regimens.

Topics: Antineoplastic Agents; Biological Products; Curcumin; Humans; Molecular Structure; Nasopharyngeal Neoplasms

To study the effects of curcumin on the proliferation, invasion, apoptosis, and radiosensitivity of the radioresistant nasopharyngeal carcinoma (NPC) C6661-IR strain as well as the potential radiosensitization mechanism.. NPC cells were continuously irradiated with different intensities of radiation to induce radiation-resistant cell lines. A plate clone formation assay was used to evaluate the effect of curcumin on the radiosensitivity of NPC cells. 3-(4,5-Dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide thiazolyl blue (MTT) assay was conducted to detect changes in cell viability. Flow cytometry was employed to analyze apoptosis percentage as well as Transwell® assay and immunofluorescence assay to observe cell invasion. Western blotting was applied to detect the expression levels of Bax, Bcl-2, and pro/cleaved-caspase 3. MiR-205-5p mimics and si-TP53INP1 were synthesized and transfected into C6661-IR cells, and the cells were then incubated with 10 μm/L curcumin. Real-time quantitative reverse transcription PCR (RT-qPCR) was used to measure miR-205-5p levels and western blotting was conducted to detect the expression of TP53INP1.. The optimal radiation dose of X-ray was 6 Gy, and this dose was used in all subsequent experiments. Curcumin treatment significantly inhibited the proliferation and invasion of C6661-IR cells, promoted apoptosis and enhanced radiosensitivity. Compared to the 0 Gy+Cur group and the 6 Gy+Cur group, the miR-205-5p levels were higher in the C6661-IR cells of the 0 Gy and 6 Gy groups. Moreover, miR-204-5p was found to directly target TP53INP1. Curcumin downregulated miR-205-5p levels and upregulated TP53INP1 expression (. Curcumin inhibited the proliferation and invasion of C6661-IR, promoted apoptosis, and enhanced its radiosensitivity to X-rays by mediating miR-205-5p/TP53INP1 expression.

Topics: Apoptosis; Carrier Proteins; Cell Line, Tumor; Cell Proliferation; Curcumin; Gene Expression Regulation, Neoplastic; Heat-Shock Proteins; Humans; MicroRNAs; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Radiation Tolerance

Systemic chemotherapy is still the primary treatment for advanced-stage nasopharyngeal carcinoma (NPC), but only limited therapeutic success has been achieved in the past decade because of drug resistance and systemic toxicity. Curcumin (Cur) is an effective alternative to chemotherapeutics because it showed remarkable therapeutic potential in the treatment of NPC. However, lack of tissue specificity and poor penetration in solid tumors are the major obstacles to effective therapy. Therefore, in this work, a self-assembled sub-30 nm therapeutic lipid nanoparticle loaded with Cur, named as Cur@α-NTP-LN, was constructed, specifically targeting scavenger receptor class B member 1 (SR-B1) and enhancing its therapeutic effects on NPC in vivo. Our results showed that Cur@α-NTP-LNs were effective and superior to free Cur on NPC cell-specific targeting, suppressing cell proliferation and inducing cell apoptosis. In vivo and ex vivo optical imaging revealed that Cur@α-NTP-LNs exerted high targeting efficiency, specifically accumulating in NPC xenograft tumors and delivering Cur into the tumor center after systemic administration. Furthermore, Cur@α-NTP-LNs exhibited a remarkable inhibitory effect on the growth of NPC subcutaneous tumors, with over 71 and 47% inhibition compared to Cur- and α-NTP-LNs-treated groups, respectively. In addition, Cur@α-NTP-LNs almost blocked NPC metastasis in a lung metastasis model of NPC and significantly improved the survival rate. Thus, the sub-30 nm Cur@α-NTP-LNs enhanced the solubility of Cur and demonstrated the ability of targeted Cur delivery into the center of the solid NPC tumor, performing synergistic inhibitory effects on the growth of NPC tumor and its metastasis with high efficiency.

Topics: Administration, Cutaneous; Animals; Apoptosis; Cell Line, Tumor; Cell Proliferation; Curcumin; Drug Carriers; Drug Delivery Systems; Humans; Liposomes; Lung Neoplasms; Mice; Nanoparticles; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Neoplasm Metastasis; Particle Size; Peptides; Solubility

Circular RNAs (circRNAs) are involved in the regulation of gene expression in different physiological and pathological processes. These macromolecules can act as microRNA (miRNA) sponges and play an important role as gene regulators throughout the circRNA-miRNA pathway. In this study, we established a radioresistance model with the nasopharyngeal carcinoma cell line CNE-2, and then analyzed the differences in the circRNAs between radioresistant and normal nasopharyngeal carcinoma cell lines using a high-throughput microarray. Tested circRNAs included 1042 upregulated and 1558 downregulated circRNAs. Relevant signaling pathways associated with the circRNAs and their target miRNAs were analyzed using bioinformatics analysis to determine the radioresistance of the differentially expressed circRNAs. Curcumin was used to treat irradiated cell lines, and changes in the circRNA before and after curcumin treatment were analyzed to investigate the radiosensitization effects of curcumin. The results showed that curcumin could regulate the circRNA-miRNA-messenger RNA network and inhibit the epidermal growth factor receptor (EGFR), signal transducers and activators of transcription 3 (STAT3), and growth factor receptor-bound protein 2 (GRB2) to achieve radiosensitization. Thus, circRNA acted as a miRNA sponge and regulated the expression of miRNA, thereby affecting EGFR, STAT3, and GRB2 expression and radiosensitization.

Topics: Cell Line, Tumor; Curcumin; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Humans; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Oligonucleotide Array Sequence Analysis; Radiation Tolerance; RNA, Circular; Signal Transduction

Curcumin (CUR) is a natural diarylheptanoid with marked anti-tumor activities. Recent investigations demonstrate that CUR combines with some other phytochemicals exerts advantages over its single application manifested as lower toxicity, higher efficacy or more significant reversal of multidrug resistance.. This study aimed to elucidate a new biflavonoid (wikstroflavone B, WFB) isolated from Wikstroemia indica and to assess the synergistic inhibition of combined CUR and WFB (CUR/WFB) on human nasopharyngeal carcinoma (NPC) cell lines proliferation and metastasis.. WFB was obtained through sequential chromatographic methods including silica gel, Sephadex LH-20 and preparative HPLC. Its structure was determined by HRESIMS, 1D and 2D NMR spectroscopic analysis. The absolute configuration of WFB was assigned through comparison of experimental and calculated optical rotation (OR) values. Changes in cellular viability, migration and invasion were assessed by MTT, colony formation, wound healing and Transwell assays. The nature of synergistic interaction of CUR/WFB was determined through the combination index (CI) method under the median-effect analysis. Expression levels of indicated mRNAs and proteins were measured by qRT-PCR and Western blotting assays, respectively.. WFB was isolated and structural elucidated. Compared with CUR or WFB used alone, CUR/WFB treatment inhibited more effectively on the cell viability, colony formation, cell migration and invasion. Both CI and dose reduction index (DRI) values indicated the significant synergistic effects existed between CUR and WFB. Besides, CUR/WFB showed the marked modulation on the genes involved in cell proliferation (survivin, cyclin D1, p53 and p21) and metastasis (MMP-2, MMP-9 and FAK). CUR/WFB treatment was also found to restrain the phosphorylation of FAK and STAT3 proteins. When pretreatment with a FAK inhibitor, the cell viability and metastasis were significantly attenuated.. The results indicate that WFB can synergistically increase the inhibitory effects of CUR on NPC cells proliferation and metastasis, and these findings may afford a rational approach for developing the antitumor medications.

Topics: Antineoplastic Combined Chemotherapy Protocols; Biflavonoids; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cell Survival; Curcumin; Focal Adhesion Kinase 1; Humans; Matrix Metalloproteinases; Molecular Structure; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Signal Transduction; STAT3 Transcription Factor; Wikstroemia

This investigation aims to study the effect of curcumin on the proliferation, cycle arrest, and apoptosis of Epstein-Barr virus- (EBV-) positive nasopharyngeal carcinoma (NPC) cells. EBV

Topics: Apoptosis; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Curcumin; Epstein-Barr Virus Nuclear Antigens; HeLa Cells; Herpesvirus 4, Human; Humans; Mitochondria; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Proteasome Endopeptidase Complex; RNA, Messenger; Signal Transduction; Ubiquitin; Virus Replication

Curcumin is a conventional Chinese medicine, which exerts a marked effect on various tumor types and suppresses tumor invasion. The present study analyzed the antineoplastic effects of curcumin on human nasopharyngeal carcinoma (NPC) cells and determined the effects of endoplasmic reticulum (ER) stress on curcumin‑induced cytotoxicity. The Cell Counting Kit‑8 assay examined the viability of SUNE1 and SUNE2 NPC cells. The Annexin V/propidium iodide staining technique was used to detect cell apoptosis and flow cytometry was used to examine cell cycle distribution. Western blotting and immunofluorescence were used to detect ER stress‑associated molecules. Furthermore, the toxic effects of curcumin treatment alongside glucose‑regulated protein 78 (GRP78) knockdown using small interfering (si)RNA, and treatment with the pan‑caspase inhibitor Z‑VAD‑FMK and the protein kinase B (AKT) inhibitor MK‑2206 were detected. The results demonstrated that curcumin markedly reduced cell viability, blocked cell cycle progression and induced apoptosis of human NPC cells. In addition, curcumin activated ER stress‑associated proteins to participate in the apoptosis of human NPC cells. siRNA‑induced knockdown of GRP78 may be able to strengthen the toxic effects of curcumin through mediating the AKT signaling pathway. These findings indicated that downregulation of GRP78 promoted the therapeutic effects of curcumin on NPC cells. The present study identified a potential, novel therapeutic method for the treatment of NPC.

Topics: Antineoplastic Agents; Apoptosis; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Survival; Curcumin; Down-Regulation; Endoplasmic Reticulum Chaperone BiP; Heat-Shock Proteins; Humans; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; RNA Interference

Topics: Carcinoma; Curcumin; Humans; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy usually associated with overexpression of both epidermal growth factor receptor (EGFR) and β-catenin. FM807 is a novel curcumin analogue with antitumor activity against both poorly and well-differentiated NPC cell lines as well as good selectivity for tumor cells. FM807 actions were shown to include inhibition of cell growth, induction of necrotic/late apoptotic cell death, and G1 arrest in NPC cells. Crucially, it exhibited potent antitumor effects both in vitro and in vivo. Binding of FM807 to the N-terminus of Hsp90 disrupted Hsp90/client complexes, resulting in degradation of the Hsp90 client protein EGFR and inhibition of the downstream Raf/MEK/ERK and PI3K/AKT pathway. FM807 also depleted levels of the intranuclear transcription factors β-catenin, Cyclin D1 and c-Myc levels by inhibiting Hsp90 chaperoned nuclear transport. In conjunction with its low toxicity in NPC xenograft mice, these results provide a sound preclinical basis for further development of FM807 as a novel therapeutic agent in the treatment of NPC.

Topics: Animals; Antineoplastic Agents; Apoptosis; beta Catenin; Blotting, Western; Cell Line, Tumor; Cell Proliferation; Curcumin; Cyclin D1; ErbB Receptors; G1 Phase Cell Cycle Checkpoints; HSP90 Heat-Shock Proteins; Humans; Male; MAP Kinase Signaling System; Mice, Inbred BALB C; Mice, Nude; Nasopharyngeal Neoplasms; Protein Binding; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; Xenograft Model Antitumor Assays

Curcumin shows growth-inhibition against tumor cells through multi-target mechanisms. Nevertheless, the poor stability and pharmacokinetics considerably limit its clinical functions. Increased effort has been put into the chemical alteration of curcumin to find potential analogues with improved bioavailability and antitumor activities. In this study, the antitumor activity of a novel curcuminoid (B63) in nasopharyngeal carcinoma (NPC) was examined. The MTT and colony formation assays were used to detect NPC cell viability and proliferation. Flow cytometry was used to detect cell cycle distribution. The Annexin V/PI staining assay and cleavage PARP and cleavage caspase-3 expression were used to examine apoptosis. Western blotting was used to examine the protein expression of endoplasmic reticulum (ER) stress pathway markers, XBP-1, ATF-4 and CHOP. The suppressive effect of B63 on tumor growth was examined in vivo by subcutaneously inoculated NPC in a tumor model using nude mice. Treatment with B63 potentially caused growth inhibition and apoptosis in NPC cells in a dose- and time-responsive manner. Its antitumor effect was associated with the ER stress activation. Nevertheless, the same dose of curcumin did not activate ER stress. In addition, knockdown of Chop attenuated B63-induced cell viability inhibition, suggesting that the apoptotic pathway is ER stress-dependent. The tumor volume and weight were significantly reduced by pretreating the NPC cells with B63 before implantation in the in vivo mouse model. B63 exhibited a more potent antitumor action than curcumin in NPC. These observations on the novel compound B63 indicate a novel candidate for NPC therapy.

Topics: Activating Transcription Factor 4; Animals; Antineoplastic Agents; Apoptosis; Carcinoma; Cell Line, Tumor; Cell Proliferation; Cell Survival; Curcumin; Dose-Response Relationship, Drug; Endoplasmic Reticulum Stress; Humans; Mice; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Time Factors; Transcription Factor CHOP; X-Box Binding Protein 1; Xenograft Model Antitumor Assays

Long non-coding RNAs (lncRNAs) are aberrantly expressed and have important functions in pathological processes. The present study investigated the lncRNA profiles and the effects of curcumin (Cur) on the radiosensitivity of nasopharyngeal carcinoma (NPC) cells. The lncRNA and mRNA profiles of each cell group were described by microarray analysis. Numerous differentially expressed genes were observed by microarrays in three cell groups. Cur significantly reversed the IR-induced lncRNA and mRNA expression signatures, shown by clustering analysis. Moreover, 116 of these IR-induced and Cur-reversed differentially expressed lncRNAs were obtained. Six lncRNAs (AF086415, AK095147, RP1-179N16.3, MUDENG, AK056098 and AK294004) were confirmed by qPCR. Furthermore, functional studies showed that lncRNA AK294004 exhibited a negative effect on cyclin D1 (CCND1), indicating that CCND1 might be a direct target of AK294004. IR-induced differentially expressed lncRNAs were reversed during Cur-enhanced radiosensitization in NPC cells, suggesting that lncRNAs have important functions in IR-induced radioresistance. Thus, Cur could serve as a good radiosensitizer.

Topics: Carcinoma; Cell Line, Tumor; Curcumin; Cyclin D1; Gene Expression Regulation, Neoplastic; Humans; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Radiation Tolerance; RNA, Long Noncoding; RNA, Messenger

Curcumin, one of the main bioactive components extracted from a traditional Chinese medicinal herb, exhibits potent anticancer activity against many types of cancer cells including nasopharyngeal carcinoma (NPC). However, the detailed molecular mechanism underlying this is not clearly understood. In this study, we showed that curcumin significantly inhibited the growth of NPC cells in a dose- and time-dependent manner as determined by MTT assays, while increasing apoptosis was also observed as measured by flow cytometry for the FITC-Annexin V and propidium iodide (PI) label and Hoechst 33258 staining. To further explore the potential mechanism, we showed that curcumin increased the phosphorylation of ERK1/2 but not p38 MAPK in a time-dependent manner, and induced protein expression of the tumor suppressors FOXO3a and p53 in a dose‑dependent manner, which were not observed in the presence of PD98059, an inhibitor of ERK1/2. Furthermore, silencing of FOXO3a and p53 genes by siRNAs overcame the inhibitory effect of curcumin on cell proliferation. Silencing or blockade of p53 using siRNA or chemical inhibitor abrogated the effect of curcumin on expression of FOXO3a protein; silencing or overexpression of FOXO3a had no further effect on curcumin-induced p53 protein expression. Furthermore, blockade of ERK1/2 and exogenous expression of FOXO3a restored the effect of curcumin on growth of cells. Together, our studies show that curcumin inhibits growth and induces apoptosis of NPC cells through ERK1/2-mediated increase in the protein expression and interaction of p53 and FOXO3a. p53 is upstream of FOXO3a, which form a regulatory loop that mediates the effect of curcumin. This study unveils a new mechanism by which curcumin inhibits the proliferation and induces apoptosis of human NPC cells.

Topics: Antineoplastic Agents; Apoptosis; Carcinoma; Cell Line, Tumor; Cell Proliferation; Curcumin; Dose-Response Relationship, Drug; Flavonoids; Forkhead Box Protein O3; Forkhead Transcription Factors; Gene Expression Regulation, Neoplastic; Humans; MAP Kinase Signaling System; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Phosphorylation; Tumor Suppressor Protein p53

Curcumin suppresses proliferation, migration, invasion, metastasis and angiogenesis and induces apoptosis by regulating multiple signalling pathways and miRNAs in a wide variety of human malignancies. miRNAs play crucial roles in various steps of carcinogenesis in nasopharyngeal carcinoma (NPC); thus, they could serve as critical therapeutic targets for NPC treatment. Curcumin could provide a novel strategy to block or induce specific miRNAs for miRNA-based gene therapies. Nevertheless, there are no reports to date on the miRNAs regulated by curcumin in NPC. In the present study, we have carried out an miRNA microarray to identify the miRNAs regulated by curcumin in NPC. Curcumin treatment down-regulated the expression of hsa-miR-125a-5p, hsa-miR-574-3p and hsa-miR-210 as determined by miRNA microarray analysis and qPCR (real-time quantitative reverse transcription-PCR). Forced expression of miR-125a-5p enhanced proliferation, migration and invasion of HONE1 cells. Primary NPC exhibited a significantly higher expression level of miR-125a-5p than healthy controls. miR-125a-5p inhibited the expression of tumour protein 53 (TP53), and curcumin treatment up-regulated the expression of TP53. Taken together, these results indicate that curcumin exerted inhibitory effects on NPC by inhibiting the expression of miR-125a-5p and, subsequently, enhancing the expression of TP53. Curcumin could provide a novel strategy to block miR-125a-5p for miRNA-based gene therapies in NPC.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Animals; Antineoplastic Agents; Cell Line, Tumor; Cell Movement; Cell Proliferation; Child; Curcumin; Female; Gene Expression Regulation, Neoplastic; Humans; Male; Mice; Mice, Nude; MicroRNAs; Middle Aged; Nasopharyngeal Neoplasms; Oligonucleotide Array Sequence Analysis; RNA Interference; Tumor Suppressor Protein p53; Xenograft Model Antitumor Assays; Young Adult

The aim of the present study was to evaluate the antitumor effects of the curcumin analogue GL63 on radioresistant nasopharyngeal carcinoma (NPC) CNE2R cells and parental CNE2 cells. The cell viability and proliferation of NPC cells were detected by MTT assay and colony formation assay. The suppressive effect on tumor growth was examined using in vivo subcutaneously inoculated NPC tumor models using nude mice. The cell cycle distribution was detected using flow cytometry. Apoptosis was examined by Hoechst 33342 and Annexin V/PI staining assay. The protein expression of endoplasmic reticulum (ER) stress pathway markers, XBP-1, ATF-4 and CHOP, were examined by western blotting. A growth inhibitory effect was observed following treatment with GL63 in a dose-dependent manner and was more potent when compared to curcumin. GL63 at 5 µM induced significant G2/M arrest and apoptosis in NPC. The tumor-suppressive activity of GL63 in NPC xenograft models was more potent when compared to curcumin. Furthermore, GL63 induced an ER stress response, upregulation of CHOP, XBP-1 and ATF-4 expression, while the same concentration of curcumin had no effect on ER stress. These results suggest that GL63 has more potent antitumor activity than curcumin, which is associated with activation of ER stress, induction of G2/M arrest and apoptosis in NPC cells.

Topics: Activating Transcription Factor 4; Animals; Antineoplastic Agents; Apoptosis; Bromobenzenes; Carcinoma; Cell Line, Tumor; Cell Proliferation; Cell Survival; Curcumin; DNA-Binding Proteins; Endoplasmic Reticulum Stress; Female; G2 Phase Cell Cycle Checkpoints; Humans; Mice; Mice, Nude; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Pentanones; Regulatory Factor X Transcription Factors; Transcription Factor CHOP; Transcription Factors; X-Box Binding Protein 1; Xenograft Model Antitumor Assays

Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus-associated malignancy that is most common in East Asia, Africa, and Alaska. Radiotherapy is the main treatment option; unfortunately, disease response to concurrent radiotherapy and chemotherapy varies among patients with NPC, and in many cases, NPC becomes resistant to radiotherapy. Our previous studies indicated that Jab1/CSN5 was overexpressed and plays a role in the pathogenesis and radiotherapy resistance in NPC. Therefore, it is important to seek for innovative therapeutics targeting Jab1/CSN5 for NPC. In this study, we explored the antitumor effect of a curcumin analogue T83 in NPC, and found T83 exhibits antitumor activity and induces radiosensitivity through inactivation of Jab1 in NPC.. NPC cell viability and proliferation were detected by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and colony formation assays. Cell cycle distribution was detected with use of flow cytometry. Apoptosis was examined by using the Annexin V/propidium iodide staining assay and cleavage poly(ADP-ribose polymerase (PARP) and cleavage caspase-3 expression. Jab1 expression was examined by Western blotting.. A growth inhibitory effect was observed with T83 treatment in a dose- and time-dependent manner. T83 significantly induced G2/M arrest and apoptosis in NPC. In addition, T83 inhibited Jab1 expression and sensitized NPC cells to radiotherapy.. Our data indicate that T83 exhibits potent inhibitory activity in NPC cells and induces radiotherapy sensitivity. Thus, T83 has translational potential as a chemopreventive or therapeutic agent for NPC.

Topics: Apoptosis; Blotting, Western; Carcinoma; Cell Line, Tumor; Cell Proliferation; Cell Survival; COP9 Signalosome Complex; Curcumin; Flow Cytometry; Humans; Immunoblotting; Intracellular Signaling Peptides and Proteins; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Peptide Hydrolases; Radiation Tolerance; Radiation-Sensitizing Agents; RNA, Small Interfering; Transfection

This study aimed to investigate the effect of Curcuma kwangsiensis polysaccharides on the viability of human nasopharyngeal carcinoma cell line CNE-2 cells, and explore the possible mechanisms. CNE-2 cells were treated with various concentrations of C. kwangsiensis polysaccharides, then the proliferation, apoptosis and the protein expression of apoptosis-related regulators p53 and Bcl-2 were assessed. The results demonstrated that C. kwangsiensis polysaccharides can significantly inhibit the proliferation of CNE-2 cells, which was possibly through the induction of apoptosis mediated by attenuating Bcl-2 expression and promoting p53 expression. The present study therefore indicates that C. kwangsiensis polysaccharides could be developed into potential drugs for nasopharyngeal carcinoma treatment.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Carcinoma; Cell Line, Tumor; Curcuma; Humans; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Polysaccharides; Proto-Oncogene Proteins c-bcl-2; Tumor Suppressor Protein p53

Curcumin, a natural pigment from a traditional Chinese herb, has been attracting extensive attention. The present study aims to investigate cell death of nasopharyngeal carcinoma (NPC) cells induced by ultrasound sonication in the presence of curcumin in vitro.. The NPC cell line CNE2 was chosen as a tumor model, and curcumin concentration was kept constant at 10 µM while the cells were subjected to ultrasound exposure for 8 s at an intensity of 0.46 W/cm(2). Cell death was evaluated using flow cytometry with annexinV-FITC and propidium iodine staining, and nuclear staining with Hoechst 33258. Mitochondrial membrane potential and intracellular reactive oxygen species (ROS) were analyzed using flow cytometry with rhodamine 123 and dichlorodihydrofluorecein diacetate staining.. Flow cytometry showed that the combination of ultrasound and curcumin significantly increased the necrotic or late apoptotic rate by up to 31.37% compared with the controls. Nuclear condensation was observed in the nuclear staining, and collapse of ΔΨm and ROS increase were found in the CNE2 cells after the treatment with curcumin and ultrasound.. The findings demonstrate that the presence of curcumin significantly enhances the ultrasound-induced cell death and ROS level, and induces the collapse of ΔΨm, suggesting that ultrasound sonication can increase the cell death of NPC cells in the presence of curcumin and that the treatment using curcumin and ultrasound together is a potential therapeutic modality in the management of malignant tumors.

Topics: Antineoplastic Agents; Carcinoma; Cell Death; Cell Line, Tumor; Combined Modality Therapy; Curcumin; Humans; Membrane Potential, Mitochondrial; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Reactive Oxygen Species; Ultrasonics

Curcumin, a natural pigment from the traditional Chinese herb, has shown promise as an efficient enhancer of ultrasound. The present study aims to investigate ultrasound-induced cellular destruction of nasopharyngeal carcinoma cells in the presence of curcumin in vitro.. Nasopharyngeal carcinoma cell line CNE2 cells were incubated by 10μm curcumin and then were treated by ultrasound for 8s at the intensity of 0.46W/cm(2). Cytotoxicity was evaluated using MTT assay and light microscopy. Mitochondrial damage was analyzed using a confocal laser scanning microcopy with Rhodamine 123 and ultrastructural changes were observed using a transmission electron microscopy (TEM).. MTT assay showed that cytotoxicity induced by ultrasound treatment alone and curcumin treatment alone was 18.16±2.37% and 24.93±8.30%, respectively. The cytotoxicity induced by the combined treatment of ultrasound and curcumin significantly increased up to 86.67±7.78%. TEM showed that microvillin disappearance, membrane blebbing, chromatin condensation, swollen mitochondria, and mitochondrial myelin-like body were observed in the cells treated by ultrasound and curcumin together. The significant collapse of mitochondrial membrane potential (MMP) was markedly observed in the CNE2 cells after the combined treatment of curcumin and ultrasound.. Our findings demonstrated that ultrasound sonication in the presence of curcumin significantly killed the CNE2 cells and induced ultrastructural damage and the dysfunction of mitochondria, suggesting that ultrasound treatment remarkably induced cellular destruction of nasopharyngeal carcinoma cells in the presence of curcumin.

Topics: Analysis of Variance; Apoptosis; Cell Line, Tumor; Curcumin; Humans; In Vitro Techniques; Microscopy, Confocal; Microscopy, Electron; Mitochondria; Nasopharyngeal Neoplasms; Ultrasonic Therapy

Curcumin, a potent candidate anticancer agent, is a dietary pigment (phenolic compound) derived from the food flavoring spice turmeric (Curcuma longa), and it has been shown to have inhibitory effects on tumor cells through anti-proliferative and proapoptotic activities. However, there is no report showing curcumin-induced apoptotic cell death in human nasopharyngeal carcinoma cells in vitro. Thus, this study was performed to elucidate whether mitochondria and caspase cascades are involved in the modulation of apoptosis and cell cycle arrest in curcumin-treated NPC-TW 076 human nasopharyngeal carcinoma cells. The effects of curcumin on cell cycle arrest and apoptosis were measured by flow cytometry, and caspase-3 activity, apoptosis-associated protein levels and its regulated molecules were studied by flow cytometric assay and immunoblots. The results indicated that curcumin-induced G2/M phase arrest was associated with a marked decrease in the protein expression of cyclin A, cyclin B and cyclin-dependent kinase 1 (Cdk1). Curcumin-induced apoptosis was accompanied with upregulation of the protein expression of Bax and downregulation of the protein levels of Bcl-2, resulting in dysfunction of mitochondria and subsequently led to cytochrome c release and sequential activation of caspase-9 and caspase-3 in NPC-TW 076 cells in a time-dependent manner. These findings revealed that mitochondria, AIF caspase-3- dependent pathways play a vital role in curcumin-induced G2/M phase arrest and apoptosis of NPC-TW 076 cells in vitro.

Topics: Acetylcysteine; Antineoplastic Agents; Apoptosis; Calcium; Carcinoma; Caspase 3; Cell Cycle; Cell Line, Tumor; Cell Survival; Curcumin; Cytosol; DNA Damage; Enzyme Activation; Free Radical Scavengers; Humans; Membrane Potential, Mitochondrial; Mitochondria; Models, Biological; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Reactive Oxygen Species; Signal Transduction

Curcumin is a natural polyphenol. It is a potent suppressor of nuclear factor kappa B (NF-kappaB). High NF-kappaB levels have suppressive effect on E-cadherin (molecule related to cell-cell adhesion) in nasopharyngeal carcinoma (NPC) cells. We hypothesized that suppressing NF-kappaB by curcumin could up-regulate E-cadherin expression in NPC cells.. NPC cell lines HK1 and HONE1 were used. Real-time quantitative PCR and Western blotting were used to examine the expression changes of NF-kappaB and E-cadherin. A mouse xenograft model was used to validate the results.. With curcumin treatment, NF-kappaB was down-regulated and E-cadherin was up-regulated in NPC cells. The negative correlation of NF-kappaB and E-cadherin was confirmed in the mouse xenograft model.. Our results suggest that curcumin could be used in preventing NPC migration by suppressing NF-kappaB and activating E-cadherin expression.

Topics: Animals; Antineoplastic Agents; Cadherins; Cell Line, Tumor; Curcumin; Female; Humans; Mice; Mice, Nude; Nasopharyngeal Neoplasms; NF-kappa B; Phenotype; RNA, Messenger; Up-Regulation; Xenograft Model Antitumor Assays

Nasopharyngeal carcinoma (NPC) is one of the common malignant cancers in China, and radiotherapy or chemotherapy is the main therapy method for NPC. Curcuminoids (or curcumin), natural antioxidants, have been recently shown to produce a potent chemopreventive action against several types of cancer. They have also displayed antioxidant and anti-inflammatory activities. In the present study, the antiproliferation and induced apoptosis effects of curcuminoids have been investigated in Detroit 562 cells (human pharynx carcinoma) and HONE-1 (human nasopharyngeal carcinoma) cells. Results indicated that curcuminoids have produced an inhibition of cell proliferation as well as the activation of apoptosis in these cancer cells. Both effects were observed to increase in proportion with the dose of curcuminoids. The DNA fragmentation, caspase-3 activation,and NF-kappaB transcriptional factor activity have been studied. By these approaches, apoptosis was induced by curcuminoids in the pharynx and nasopharyngeal cancer cells via caspase-3-dependent pathway. However, a different dependency has been observed, whereas proliferation inhibition and apoptosis depend upon the amount of curcuminoid treatment in the cancer cells.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Caspases; Cell Division; Cell Line, Tumor; Curcumin; DNA Fragmentation; Dose-Response Relationship, Drug; Humans; Nasopharyngeal Neoplasms; NF-kappa B; Pharyngeal Neoplasms

Nasopharyngeal carcinoma (NPC) is highly prevalent in Southern China. Radiotherapy is the primary treatment of NPC, but the rate of tumor recurrence is significant. Photodynamic therapy (PDT) and the use of natural compounds become one of the new approaches in the investigation of NPC treatment. PDT is an alternate method of cancer treatment while curcumin (CUR) is a compound derived from the traditional Chinese medicinal (TCM) herbs. The purpose of the study focuses on the photodynamic effect of CUR on one of the NPC cell lines, NPC/CNE2. Cytotoxicity and photocytotoxicity of CUR were evaluated by 3-(4,5-dimthyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay. Uptake kinetics of CUR in NPC/CNE2 was examined by flow cytometry. The mode of cell death induced by CUR was studied by fluorescence microscopy. Summarizing the results, CUR showed dark cytotoxicity as well as photocytotoxic effects on NPC/CNE2 cells. LC50 of CUR in the dark was about 16 microM. The cytotoxicity of CUR was enhanced by the irradiation of visible light and blue filtered light (maximum transmittance at 300 approximately 400 nm) with light doses of 300 kJ/m2 and 60 kJ/m2 respectively. NPC/CNE2 was found to rapidly take up CUR in the first hour of incubation, and the uptake kinetics steadily increased to a plateau level after 20 hr of incubation. Cell shrinkage and membrane bledding appeared under the observation of fluorescence microscopy. Such evidences proved that CUR might induce apoptosis on NPC/CNE2 cells. The preliminary study confirmed that CUR demonstrated dark cytotoxicity and photocytotoxicty to NPC/CNE2. The mode of action is likely to be induced by apoptotic pathway. CUR may be developed as a potential photosensitizer as well as a chemotherapeutic agent in clinical application.

Topics: Apoptosis; Carcinoma, Squamous Cell; Cell Line, Tumor; Curcumin; Humans; Nasopharyngeal Neoplasms; Photochemotherapy; Photosensitizing Agents

To investigate the mechanism underlying the curcumin-induced apoptosis of nasopharyngeal carcinoma (NPC) cell line NCE cells.. The characteristics of apoptosis were identified by observation acridine orange and ethidium bromide stains, ultrastructure assay, DNA fragmentation assay and TdT-mediated dUTP nick end labeling method (TUNEL). Mitochondrial membrane potential (delta psi m), activity of caspase-3, cytosol cytochrome C and expression of gene Fas were determined by flow cytometry (FCM), Western Blot and reverse transcription-polymerase chain reaction (RT-PCR).. Several evidences of apoptosis were obtained from curcumin-treated NCE cells by acridine orange and ethidium bromide stains, ultrastructure identification, DNA fragmentation assay and TUNEL staining. And the mean TUNEL-positive rates increased significantly at the 3 different time points (12 h, 24 h and 48 h; 25.6%, 40.3% and 54.5%, respectively). In the curcumin-treated-groups, delta psi m altered significantly and the positive rates increased in a time-dependent manner. At the 3 different time points, the mean positive rates were 26.8%, 42.3% and 68.2%, respectively. When caspase-3 activity was detected, 80.5% cells presented proteases activities after 12 h incubation with curcumin. Western Blot analysis showed that cytoplasmic cytochrome C increased significantly after incubation with curcumin. Flow cytometry and RT-PCR analysis showed that curcumin could up-regulate the Fas expression in time-depended manner , the positive rates of Fas protein increased from 33.6% to 89.9%.. Curcumin induced apoptosis of NCE cells both through mitochondria-dependent pathway and death receptor pathway.

Topics: Apoptosis; Caspase 3; Cell Line, Tumor; Curcumin; fas Receptor; Humans; Membrane Potential, Mitochondrial; Nasopharyngeal Neoplasms

Nasopharyngeal carcinoma (NPC) is a common malignant tumor in southern China. Radiotherapy is a major therapy for NPC in early phase,while proper chemotherapy is necessary for NPC in late phase. Some chemotherapeutic drugs have been used to treat tumors by inducing apoptosis of tumor cells. This study was to investigate effects of curcumin on proliferation,and apoptosis of NPC cell line CNE-2Z.. CNE-2Z cells were treated with different concentrations of curcumin, inhibition rates of cell proliferation,and IC(50) of curcumin were detected by MTT method. Cell apoptosis was analyzed by flow cytometry (FCM), agarose gel electrophoresis,and Hoechst33258-PI fluorescence staining.. Proliferation of CNE-2Z cells was inhibited obviously by curcumin in dose- and time-dependent manners. IC(50) of curcumin to CNE-2Z cells at 24,48,and 72 h were (24.05+/-0.47),(19.20+/-0.17),and (7.35+/-0.50) micromol/L, respectively. After treated with 5,10,and 20 micromol/L of curcumin for 24 h, apoptotic rates of CNE-2Z cells were (4.9+/-3.2)%,(10.7+/-2.7)%, and (14.7+/-0.5)%, respectively. After treated with 10,20 micromol/L of curcumin for 24 h, morphologic changes, such as chromatin shrinkage,nuclear condensation,and chromatin fragmentation,were observed in CNE-2Z cells by fluorescent staining, a fragmented DNA ladder was detected by electrophoresis.. Curcumin may induce apoptosis, and inhibit proliferation of CNE-2Z cells.

Topics: Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Cell Proliferation; Curcuma; Curcumin; Dose-Response Relationship, Drug; Humans; Nasopharyngeal Neoplasms; Plants, Medicinal; Time Factors

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; B-Lymphocytes; Carcinoma, Hepatocellular; Curcumin; Dietary Supplements; Herpesvirus 4, Human; Humans; Liver Neoplasms; Mice; Mice, Inbred C3H; Nasopharyngeal Neoplasms