curcumin and Uterine-Neoplasms

Fibroids are the most common tumor of the female reproductive tract, but approved medical treatments are limited. Patients demand uterine-sparing treatments which preserve fertility and avoid surgery. We systematically reviewed PubMed and Cochrane databases from January 1985 to November 2015 for evidence-based medical therapies for fibroids in the context of disease prevention, treatment of early disease, treatment of symptomatic disease, and preoperative management. We identified 2182 studies, of which 52 studies met inclusion and exclusion criteria. Published data affirm the efficacy of multiple agents, which are promising avenues for the development of medical alternatives to surgery.

Topics: Androgens; Aromatase Inhibitors; Contraceptive Agents, Female; Contraceptives, Oral, Combined; Curcumin; Delayed-Action Preparations; Drugs, Chinese Herbal; Estradiol; Estrenes; Estrogen Receptor Antagonists; Evidence-Based Medicine; Female; Fulvestrant; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Intrauterine Devices, Medicated; Leiomyoma; Levonorgestrel; Medroxyprogesterone Acetate; Mifepristone; Neoadjuvant Therapy; Norpregnadienes; Oximes; Plant Extracts; Receptors, Progesterone; Selective Estrogen Receptor Modulators; Tea; Uterine Myomectomy; Uterine Neoplasms; Vitamin D; Vitamins

To determine whether a curcumin-supplemented diet would prevent and/or treat uterine leiomyoma growth in our mouse xenograft model.. Animal study.. Laboratory study.. N/A.. Curcumin-supplemented diet.. Dietary intake, blood concentrations, tumor size, extracellular matrix protein concentrations, apoptosis markers.. We found that curcumin was well tolerated as a dietary supplement, free curcumin and its metabolites were detected in the serum, and exposure resulted in approximately 60% less leiomyoma xenograft growth as well as dissolution of the peripheral extracellular matrix architecture of the xenografts. The production of matrix proteins, including collagens, decreased, whereas the number of apoptotic cells in the xenografts increased. Additionally, when xenografts were placed in a uterine intramural location, we found a significantly increased apoptotic response to curcumin in the diet.. Mice on a diet supplemented with curcumin could achieve serum concentrations sufficient to regulate human leiomyoma xenograft growth, and curcumin could play both preventive and curative roles in the treatment of uterine leiomyoma as an oral nutritional supplement.

Topics: Animals; Curcumin; Extracellular Matrix; Female; Heterografts; Humans; Leiomyoma; Mice; Solubility; Uterine Neoplasms

Rhizoma Curcumae and Rhizoma Sparganii (RCRS), a celebrated traditional Chinese medicine drug pair, has been used to treat hysteromyoma (HY).. We aimed to identify the endogenous biomarkers of RCRS against HY.. HY rat model was established by injecting intramuscularly estradiol benzoate and progesterone injection from inner thigh in sequence. Body weight, uterus morphological indexes, immunohistochemistry (IHC) and hematoxylin and eosin (HE) staining experiments were used to evaluate the efficacy of RCRS (The rats were treated with RCRS extract, which was made by soxhlet reflux method. The rats were administrated intragastrically with 2 mL of RCRS extract). UPLC-Q-TOF-MS based metabonomics was adopted to analyze the serum and urine biomarkers from HY rats before and after RCRS treatment. Principle component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were utilized to identify differences of metabolic profiles in rats among the four groups.. 16 potential biomarkers from serum and 18 potential biomarkers from urine in both positive and negative mass spectrometry detection modes were identified, primarily related to Linoleic acid metabolism and Glyoxylate and dicarboxylate metabolism. RCRS drug pair has therapeutic effects on rats with HY via the regulation of multiple metabolic pathways.. This study provides a useful method to get insight into the integrated metabonomic mechanism of RCRS drug pair on HY rats.

Topics: Animals; Biomarkers; Chromatography, High Pressure Liquid; Curcuma; Female; Mass Spectrometry; Metabolome; Metabolomics; Plant Extracts; Rats, Sprague-Dawley; Rhizome; Typhaceae; Uterine Neoplasms

The aim of this study was to elucidate the concise effects of a traditional herb pair, Curcumae rhizoma-Sparganii rhizoma (CRSR), on uterine leiomyoma (UL) by analyzing transcriptional profiling. The UL rat model was made by intramuscular injection of progesterone and gavage administration of diethylstilbestrol. From 11 weeks of the establishment of the model, rats of the UL+CRSR group were gavaged daily with CRSR (6.67 g/kg). The serum concentrations of progesterone (P) and estradiol (E2) were determined by radioimmunoassay, the uterine index was measured by caliper measurement, and the pathological status was observed by hematoxylin and eosin stain. Gene expression profiling was checked by NimbleGen Rat Gene Expression Microarrays. The results indicated that the uterine mass of UL+CRSR rats was significantly shrunk and serum P and E2 levels significantly reduced compared to UL animals and nearly to the level of normal rats. Results of microarrays displayed the extensive inhibition of CRSR upon the expression of proliferation and deposition of extracellular matrix (ECM)-related genes, and significantly regulated a wide range of metabolism disorders. Furthermore, CRSR extensively regulated key pathways of the UL process, such as MAPK, PPAR, Notch, and TGF-β/Smad. Regulation of the crucial pathways for the UL process and ECM metabolism may be the underlying mechanisms of CRSR treatment. Further studies will provide clear clues for effectively treating UL with CRSR.

Topics: Animals; Curcuma; Disease Models, Animal; Female; Gene Expression Regulation, Neoplastic; Leiomyoma; Oligonucleotide Array Sequence Analysis; Plant Extracts; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Rhizome; Transcription Factors; Uterine Neoplasms

Uterine leiomyosarcomas generally do not respond well to standard chemotherapy. We previously demonstrated that curcumin, the active ingredient derived from the herb Curcuma longa, inhibits uterine leiomyosarcoma cells in vitro via the inhibition of the AKT-mammalian target of rapamycin (mTOR) pathway. As a preclinical investigation, we performed an in vivo study using female nude mice to confirm the therapeutic potential of curcumin against uterine leiomyosarcoma.. Human leiomyosarcoma cells, SK-UT-1, were inoculated in female nude mice to establish subcutaneous tumors. Either vehicle control or 250 mg/kg curcumin was administered intraperitoneally every day for 14 consecutive days, and the mice were then killed. The tumors were measured every 2-3 days. The tumors were processed for immunohistochemical analyses to detect total AKT, phosphorylated AKT, total mTOR, phosphorylated mTOR, and phosphorylated S6. To detect apoptosis, the tumors were stained for cleaved PARP and TUNEL. Ki-67 immunohistochemistry was performed to determine cell viability of the tumors.. Compared with the control, curcumin reduced uterine leiomyosarcoma tumor volume and mass significantly with a concordant decrease in mTOR and S6 phosphorylation. However, AKT phosphorylation was not significantly altered. Cleaved PARP and TUNEL staining increased significantly with curcumin administration, indicating the induction of apoptosis. There was no difference in Ki-67 staining between the two groups.. Curcumin inhibited uterine leiomyosarcoma tumor growth in vivo by targeting the AKT-mTOR pathway for inhibition.

Topics: Animals; Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Curcumin; Female; Humans; Ki-67 Antigen; Leiomyosarcoma; Mice; Mice, Inbred BALB C; Phosphorylation; Proto-Oncogene Proteins c-akt; Signal Transduction; TOR Serine-Threonine Kinases; Uterine Neoplasms; Xenograft Model Antitumor Assays

Uterine leiomyosarcoma (LMS) has an unfavorable response to standard chemotherapy. A natural occurring compound, curcumin, has been shown to have inhibitory effects on cancers. We previously demonstrated that curcumin reduced uterine LMS cell proliferation by targeting the AKT-mTOR pathway and activating apoptosis. To further explore the anticancer effect of curcumin, we investigated the efficacy of curcumin on autophagy in LMS cells.. Cell proliferation in human uterine LMS cell lines, SKN and SK-UT-1, was assessed after exposure to rapamycin or curcumin. Autophagy was detected by Western blotting for light chain 3 and sequestosome 1 (SQSTM1/p62) expression. Apoptosis was confirmed by Western blotting for cleaved poly (ADP-ribose) polymerase (PARP).. Both rapamycin and curcumin potently inhibited SKN and SK-UT-1 cell proliferation in a dose-dependent manner. Curcumin induced autophagy and apoptosis in SKN and SK-UT-1 cells, whereas rapamycin, a specific mTOR inhibitor, did not. Curcumin increased extracellular signal-regulated kinase 1/2 activity in both SKN and SK-UT-1 cells, whereas PD98059, an MEK1 inhibitor, inhibited both the extracellular signal-regulated kinase 1/2 pathway and curcumin-induced autophagy.. These experimental findings suggest that curcumin is a potent inhibitor of cell proliferation in uterine LMS and provide new insights about ongoing signaling events leading to the possible development of a new therapeutic agent.

Topics: Antineoplastic Agents; Apoptosis; Autophagy; Blotting, Western; Cell Proliferation; Curcumin; Enzyme Inhibitors; Extracellular Signal-Regulated MAP Kinases; Female; Humans; Leiomyosarcoma; Phosphorylation; Proto-Oncogene Proteins c-akt; Signal Transduction; TOR Serine-Threonine Kinases; Tumor Cells, Cultured; Uterine Neoplasms

Uterine leiomyosarcoma (LMS) has an unfavorable response to standard chemotherapeutic regimens. Two natural occurring compounds, curcumin and epigallocatechin gallate (EGCG), are reported to have anti-cancer activity. We previously reported that curcumin reduced uterine LMS cell proliferation by targeting the AKT-mTOR pathway. However, challenges remain in overcoming curcumin's low bioavailability.. The human LMS cell line SKN was used. The effect of EGCG, curcumin or their combination on cell growth was detected by MTS assay. Their effect on AKT, mTOR, and S6 was detected by Western blotting. The induction of apoptosis was determined by Western blotting using cleaved-PARP specific antibody, caspase-3 activity and TUNEL assay. Intracellular curcumin level was determined by a spectrophotometric method. Antibody against EGCG cell surface receptor, 67-kDa laminin receptor (67LR), was used to investigate the role of the receptor in curcumin's increased potency by EGCG.. In this study, we showed that the combination of EGCG and curcumin significantly reduced SKN cell proliferation more than either drug alone. The combination inhibited AKT, mTOR, and S6 phosphorylation, and induced apoptosis at a much lower curcumin concentration than previously reported. EGCG enhanced the incorporation of curcumin. 67LR antibody partially rescued cell proliferation suppression by the combination treatment, but was not involved in the EGCG-enhanced intracellular incorporation of curcumin.. EGCG significantly lowered the concentration of curcumin required to inhibit the AKT-mTOR pathway, reduce cell proliferation and induce apoptosis in uterine LMS cells by enhancing intracellular incorporation of curcumin, but the process was independent of 67LR.

Topics: Apoptosis; Biological Availability; Catechin; Cell Line, Tumor; Cell Proliferation; Curcumin; Drug Synergism; Female; Humans; Leiomyosarcoma; Oncogene Protein v-akt; Receptors, Laminin; Ribosomal Protein S6 Kinases; Signal Transduction; TOR Serine-Threonine Kinases; Uterine Neoplasms

Uterine leiomyomas are the most common gynaecological benign tumour and greatly affect reproductive health and wellbeing. They are the predominant indication for hysterectomy in premenopausal women. Curcumin, a well-known component of turmeric, has been reported to prevent various diseases such as cancer, diabetes and obesity. Previous study reported that curcumin represses the proliferation of several tumour cells. However, there has not been a precise characterisation of the curcumin-induced inhibition of uterine leiomyoma cells. In this study, we investigated the inhibitory effect of curcumin on leiomyoma cells proliferation.. Eker rat-derived uterine leiomyoma cell lines (ELT-3 cells) were used. Cell proliferation was assessed by counting the number of cells and MTS assay. The activation of peroxisome proliferator-activated receptor-gamma (PPARγ) was evaluated by luciferase assay.. We found that curcumin significantly inhibited ELT-3 cell proliferation. PPARγ was expressed in ELT-3 cells and curcumin acted as a PPARγ ligand. This inhibitory effect of curcumin was attenuated by the treatment of cells with PPARγ antagonist.. These experimental findings in vitro show that the inhibitory effect of curcumin on ELT-3 cell proliferation occurs through the activation of PPARγ. Curcumin may be useful as an alternative therapy for uterine leiomyoma.

Topics: Animals; Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Cell Proliferation; Curcumin; Female; Leiomyoma; PPAR gamma; Rats; Uterine Neoplasms; Uterus

Uterine leiomyosarcoma generally has an unfavorable response to standard chemotherapy. The loss of PTEN which results in constitutive AKT-mTOR activation causes an increase in leiomyosarcoma formation in mice. The active ingredient derived from the herb Curcuma longa, curcumin, shows antitumor properties in a variety of cancer cell lines by altering a number of oncogenic pathways. To explore the possibility of curcumin as an alternative to standard chemotherapy, we decided to investigate curcumin's antitumor effect on uterine leiomyosarcoma cells.. Human leiomyosarcoma cell lines, SKN and SK-UT-1, were cultured for in vitro experiments. Rapamycin or curcumin was added in different doses and their effect on cell growth was detected by MTS assay. The influence of rapamycin or curcumin on AKT, mTOR, p70S6 and S6 phosphorylation and protein expression was detected by Western Blotting. The ability of rapamycin or curcumin to induce apoptosis was determined by Western blotting using cleaved-PARP specific antibody, Caspase-3 activity assay and TUNEL assay.. Both rapamycin and curcumin significantly reduced SKN cell proliferation. Curcumin inhibited mTOR, p70S6 and S6 phosphorylation similar with rapamycin. Cleaved PARP, caspase-3 activity and DNA fragmentation increased proportional with curcumin concentration. At a high concentration, curcumin significantly induced apoptosis in SKN cells, but not rapamycin.. Curcumin inhibited uterine leiomyosarcoma cells' growth by targeting the AKT-mTOR pathway for inhibition. However, rapamycin, a specific mTOR inhibitor, did not induce apoptosis in SKN cells unlike curcumin that also has a pro-apoptotic potential in SKN cells.

Topics: AMP-Activated Protein Kinases; Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Cell Survival; Curcumin; Dose-Response Relationship, Drug; Enzyme Activation; Female; Humans; Leiomyosarcoma; Oncogene Protein v-akt; Signal Transduction; Sirolimus; TOR Serine-Threonine Kinases; Uterine Neoplasms