Cytotoxic Effects Of Curcumin Research Articles

The Cytotoxic Effect of Curcumin in Rhabdomyosarcoma Is Associated with the Modulation of AMPK, AKT/mTOR, STAT, and p53 Signaling.

Approximately 7% of cancers arising in children and 1% of those arising in adults are soft tissue sarcomas (STS). Of these malignancies, rhabdomyosarcoma (RMS) is the most common. RMS survival rates using current therapeutic protocols have remained largely unchanged in the past decade. Thus, it is imperative that the main molecular drivers in RMS tumorigenesis are defined so that more precise, effective, and less toxic therapies can be designed. Curcumin, a common herbal supplement derived from plants of the Curcuma longa species, has an exceptionally low dietary biotoxicity profile and has demonstrated anti-tumorigenic benefits in vitro. In this study, the anti-tumorigenic activity of curcumin was assessed in rhabdomyosarcoma cell lines and used to identify the major pathways responsible for curcumin's anti-tumorigenic effects. Curcumin treatment resulted in cell cycle arrest, inhibited cell migration and colony forming potential, and induced apoptotic cell death. Proteome profiler array analysis demonstrated that curcumin treatment primarily influenced flux through the AKT-mammalian target of rapamycin (mTOR), signal transducer and activator of transcription (STAT), AMP-dependent kinase (AMPK), and p53 associated pathways in a rhabdomyosarcoma subtype-specific manner. Thus, the strategic, combinational therapeutic targeting of these pathways may present the best option to treat this group of tumors.

Supporting the Wound Healing Process—Curcumin, Resveratrol and Baicalin in In Vitro Wound Healing Studies

The purpose of the investigation was to evaluate the effect of the selected bioflavonoids curcumin, resveratrol and baicalin on the wound healing process in an in vitro model. In the study, Balb3t3 and L929 cell lines were used. The first step was the evaluation of the cytotoxicity of the substances tested (MTT assay). Then, using the scratch test (ST), the influence of bioflavonoids on the healing process was evaluated in an in vitro model. The second stage of the work was a mathematical analysis of the results obtained. On the basis of experimental data, the parameters of the Brian and Cousens model were determined in order to determine the maximum value of the cellular and metabolic response that occurs for the examined range of concentrations of selected bioflavonoids. In the MTT assays, no cytotoxic effect of curcumin, resveratrol and baicalin was observed in selected concentrations, while in the ST tests for selected substances, a stimulatory effect was observed on the cell division rate regardless of the cell lines tested. The results obtained encourage further research on the use of substances of natural origin to support the wound healing process.

Anti-migratory effect of curcumin on A-549 lung cancer cells via epigenetic reprogramming of RECK/ matrix metalloproteinase axis.

The aim of this study was to investigate theeffects of curcumin on the viability, migration, andapoptosis of A549 lung cancer cells. Furthermore, RECK/MMPs axis as a probable regulator of cancer cell migration was assessed. In this study, effect of curcumin on viability changes, cell migration, and percentage of apoptosis of A549 non-small cell lung carcinoma was examined. The methylation status of RECK gene was investigated using MS-HRM technique. Moreover, expression changes of genes involved in apoptosis and migration (including CASP3, CASP8, CASP9, BAX, BCL2, MMP9, MMP2, and RECK) were investigated by quantitative Real-Time PCR. The results of MTT assay showed that the cytotoxic effect of curcumin was in a dose dependent manner. Flow cytometry results demonstrated a significant increase in thepercentage of apoptotic cells in curcumin treated group. In addition, curcumin inhibited migration rate in lung cancer cells. qRT-PCR revealed that expression of the candidate genes was in line with suppressed growth andmigration. This could be due to, decreased methylation ofthe RECK gene promoter after curcumin treatment. Curcumin inhibited lung cancer cells through various molecular pathways. RECK/MMPs axis as a regulator of cancer cell migration was modulated after curcumin treatment and invasion of lung cancer cells was decreased.

Transcriptome profiling of curcumin-treated T47D human breast cancer cells by a system-based approach

A systemic approach provides a comprehensive scheme from the molecular regulatory mechanism of drugs in living systems. This study investigated the regulatory mechanism of curcumin in breast cancer cells by analyzing the transcriptome alterations in T47D breast cancer cells. For this purpose, the cytotoxic effect of curcumin was evaluated by MTT assay after treating T47D cells with 0–50 μM concentration of curcumin. Furthermore, transcriptome analysis was performed using RNA sequencing to find differentially expressed genes following curcumin treatment in T47D cells. Transcription factor and microRNA profiles related to curcumin gene signature were retrieved from related databases. A system-based network analysis was performed to deepen our understanding of the curcumin mechanism of action in T47D cells. In an independent analysis, a publicly available microarray dataset including gene expression and clinical data was used to evaluate the prognostic power of curcumin signature and its relation with patients' outcomes by the Cox model. Our results suggest that curcumin triggers cell death-related pathways and regulates the metabolism of lipids and apoptotic processes in T47D cells. Curcumin signature had significant prognostic power. Regulatory network analyses found specific proteins, microRNAs and transcription factors as the hub nodes, which corresponded to the effects of curcumin treatment. This work provides a picture of the cytotoxicity mechanism of curcumin and potential therapeutic targets for treatment optimization of breast cancer.

The antiproliferative and cytotoxic effects of curcumin on human cervical cancer Hep2C cell line

The antiproliferative and cytotoxic effects of curcumin on human cervical cancer Hep2C cell line

The ability of the natural chemoprophylactic agent curcumin to function as an effective UV photosensitiser

It is known that some plant polyphenols and alkaloids can act as effective photosensitisers of UV radiation. This phenomenon can enhance both therapeutic and side effects. Since there is no information regarding curcuminoids on their ability to function as UV photosensitisers, this work investigated the effect of UV radiation on the cytotoxic effect of curcumin, as well as its nanostructured forms, against keratinocytes of the HaCaT line and cancer cells MDA-MB-231. The results obtained indicate that curcumin is an effective photosensitiser capable of initiating photochemical reactions under the influence of UV radiation of the A and B range, which lead to the formation of chemically active intermediates, disruption of membrane integrity and cell death. When curcumin is incorporated into nanostructures based on polyallylamine hydrochloride /polystyrene sulfate and chitosan /dextran sulfate, its ability to function as a UV photosensitiser is retained.

Immunological responses and anti-tumor effects of HPV16/18 L1-L2-E7 multiepitope fusion construct along with curcumin and nanocurcumin in C57BL/6 mouse model

AimsHuman papillomavirus (HPV) L1, L2 and E7 proteins were used as target antigens for development of preventive and therapeutic vaccines. Moreover, linkage of antigens to heat shock proteins (HSPs) could enhance the potency of vaccines. Curcumin and nanocurcumin compounds were suggested as the chemopreventive and chemotherapeutic agents against cancer. In this study, two multiepitope DNA and peptide-based vaccine constructs (L1-L2-E7 and HSP70-L1-L2-E7) were used along with curcumin and nanocurcumin to evaluate immune responses, and protective/therapeutic effects in tumor mouse model. Main methodsAt first, the multiepitope L1-L2-E7 and HSP70-L1-L2-E7 fusion genes were subcloned in eukaryotic and prokaryotic expression vectors. The recombinant multiepitope peptides were generated in E. coli strain. Then, the cytotoxic effects of curcumin and nanocurcumin were evaluated on HEK-293 T non-cancerous and C3 cancerous cells. Finally, mice vaccination was performed using different regimens. Curcumin and nanocurcumin compounds were administered alone or along with different vaccine constructs. Key findingsOur data indicated that the use of nanocurcumin along with the multiepitope HSP70-L1-L2-E7 vaccine construct could completely protect mice against HPV-related C3 tumor cells, and eradicate tumors in a therapeutic test. Furthermore, nanocurcumin showed higher protection than curcumin alone. Generally, curcumin and nanocurcumin compounds could reduce tumor growth synergistically with the multiepitope vaccine constructs, but they did not influence the immune responses in different regimens. SignificanceThese data demonstrated that the designed multiepitope vaccine constructs along with curcumin and nanocurcumin can be used as a promising method for HPV vaccine development.

The anti-proliferative and apoptotic effects of curcumin on feline mammary gland tumor cells in vitro.

Feline mammary gland tumors (FMGTs) are the third most diagnosed tumors in cats. Feline mammary gland tumors have aggressive biological behavior and poor response to both surgical and medical treatments, thus, new therapeutic approaches are essential to improve. Curcumin (CUR) is a polyphenol component exhibiting anti-cancer effects and induces apoptosis through different mechanisms especially in human breast cancer. However, there is no study investigating the effects of CUR on FMGTs. The aim of this study was to determine the anti-proliferative and apoptotic effects of CUR on primary cell lines from FMGT tissue samples of two cases classified as carcinoma-simple, tubular type (grade III). The cytotoxic effect of CUR was determined by water-soluble tetrazolium salt-1 (WST-1) assay. Annexin V, cell cycle, and acridine orange (AO) analyses were performed to determine the apoptotic effect of CUR. Our results showed that CUR had an anti-proliferative and apoptotic effect through induction of apoptosis and cell cycle arrest (G0/G1) on FMGT cells. Therefore, this is the first study that shows the effects of CUR on FMGTs. However, further molecular studies are required to compare the effects of CUR on different histopathological phenotypes and to determine the further molecular mechanisms including the potential apoptotic and cellular pathways affected by CUR.

In vitro antibacterial activity of curcumin-meropenem combination against extensively drug-resistant (XDR)bacteria isolated from burn wound infections.

Burn wound infection is a severe complication of thermal injury. Patients with severe burn injuries need urgent care to diminish complications after severe burns. Wound infections are commonly considered one of the most serious burn complications, particularly those that are caused by extensively drug-resistant (XDR) bacteria with few therapeutic choices. The objective of this study was to determine in vitro activity of meropenem and curcumin, alone and in combination, against antibiotic-susceptible Gram-positive, and antibiotic-resistant and antibiotic susceptible gram-negative bacteria isolated from burn wound infections. The antimicrobial activity of meropenem and curcumin was investigated alone and in combination, against antibiotic-susceptible and antibiotic-resistant bacterial (XDR) strains isolated from burn patients. In addition, the cytotoxic effect of curcumin on human's epithelial cell lines, was determined. In this study, minimum inhibitory concentrations of meropenem decreased considerably in the presence of curcumin (2- to 16-fold reductions), with synergy observed. Curcumin exerted no cytotoxic effect at concentrations 256-512 µg/ml on human epithelial cell lines. We suggest that curcumin-antibiotic combinations may provide an alternative approach for treating infections with multidrug-resistant (MDR) and extensively drug-resistant (XDR) bacteria.

Curcumin inhibits the lymphangiogenesis of gastric cancer cells by inhibiton of HMGB1/VEGF-D signaling.

Accumulating evidence shows that curcumin exerts antitumor activities in a variety of malignancies. High mobility group box 1 (HMGB1) is associated with vascular endothelial growth factor D (VEGF-D)–induced lymphangiogenesis and tumor metastasis in gastric cancer. However, the molecular mechanisms by which curcumin regulates HMGB1-mediated lymphangiogenesis in gastric cancer remain unclear. In this study, the cytotoxic effects of curcumin were investigated in gastric cancer AGS and SGC-7901 cell lines by MTT assay, and curcumin-induced morphological changes and cell apoptosis were assessed by using flow cytometry analysis and caspase-3 activity. The effects of curcumin on HMGB1 and VEGF-D expression were examined by reverse transcription polymerase chain reaction (RT-PCR) and western blot analysis. As a result, we found that curcumin decreased cell viability and caused a dose-dependent cell apoptosis through the activation of caspase-3. The mRNA and protein expression levels of HMGB1 and VEGF-D were significantly eliminated by curcumin administration. Pre-treatment with the recombinant HMGB1 (rHMGB1) markedly abolished curcumin-reduced VEGF-D expression. Our findings suggested that curcumin might exert anti-lymphangiogenesis in gastric cancer by inhibition of HMGB1/VEGF-D signaling.

Curcumin-induced autophagy and nucleophagy in Spodoptera frugiperda Sf9 insect cells occur via PI3K/AKT/TOR pathways.

Compounds from plants or microbes are important resources for new natural pesticides against a wide variety of pests. The growing attention on the role of autophagy (type II cell death) in regulation of insect toxicology has propelled researchers to investigate autophagic cell death pathways. Our previous study proved that the cytotoxic effect of curcumin in Spodoptera frugiperda cells is regulated by autophagy. However, the signaling pathways and molecular mechanisms had not been determined. The current study elucidates curcumin inhibition of survival signaling by blocking the activation of PI3K/AKT/TOR pathways to induce autophagy in S. frugiperda cells. The result demonstrates that nucleophagy associated with cell death following the curcumin treatment. Following the curcumin treatment, Atg8/LC3 immunostaining in both nucleus and cytoplasm was markedly increased. Further, messenger RNA expression level of Atg8 and Atg1 genes regulation by curcumin was examined using quantitative reverse transcription polymerase chain reaction, and the result exhibited increased level of expression after curcumin treatment in a time-dependent manner. Our current study provides new insights to the autophagy occurring via PI3K/AKT/TOR pathways in S. frugiperda Sf9 insect cells induced by curcumin. Taken together, our results show for the first time that curcumin induced nucleophagy in lepidopteron insect cell line.

Genotoxicity and cytotoxicity analysis of curcumin and sunset yellow in human lymphocyte culture.

Genotoxic and cytotoxic effects of curcumin and sunset yellow were tested by the chromosome aberration analysis and cytokinesis-block micronucleus cytome assay in human lymphocyte culture. Water solutions of food dyes, in concentrations of 1, 2, 4 and 8 mM, were added to the cultures at the beginning of the cultivation period. Concentrations of 4 and 8 mM of sunset yellow induced significant increase in frequencies of cells with chromosome aberrations. Tested concentrations of sunset yellow significantly associated with frequencies of structural aberrations, chromatid-type aberrations, total aberrant cells and micronuclei showing considerable dose dependent clastogenic activity. In higher analyzed concentrations, curcumin significantly increased only nuclear buds frequency, suggesting its potential genotoxicity, while sunset yellow showed dose-dependent genotoxic potential. Obtained results point toward favorization of natural coloring agents in food consumption and emphasize the need of controlled use of food colorants.

Curcumin inhibits bladder cancer progression via regulation of β-catenin expression.

Bladder cancer has a considerable morbidity and mortality impact with particularly poor prognosis. Curcumin has been recently noticed as a polyphenolic compound separated from turmeric to regulate tumor progression. However, the precise molecular mechanism by which curcumin inhibits the invasion and metastasis of bladder cancer cells is not fully elucidated. In this study, we investigate the effect of curcumin on the bladder cancer as well as possible mechanisms of curcumin. The expression of β-catenin was detected by quantitative real-time polymerase chain reaction and immunohistochemical analysis in a series of bladder cancer tissues. In addition, bladder cancer cell lines T24 and 5637 cells were treated with different concentrations of curcumin. The cytotoxic effect of curcumin on cell proliferation of T24 and 5637 cells was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The migration and invasion capacity of T24 and 5637 cells were measured by transwell assay. The effects of curcumin on expression levels of β-catenin and epithelial-mesenchymal transition marker were determined by western blotting. The β-catenin expression was significantly upregulated in bladder cancer tissues when compared with corresponding peri-tumor tissues. Furthermore, curcumin inhibited the cell proliferation of T24 and 5637 cells, and curcumin reduced the migration and invasive ability of T24 and 5637 cells via regulating β-catenin expression and reversing epithelial-mesenchymal transition. Curcumin may be a new drug for bladder cancer.

Mechanism of reversal of multidrug resistance by curcumin in human colorectal cancer cell line HCT-8/5-FU.

Since there are no studies on the reversal of multidrug resistance by curcumin in the human colorectal cancer cell line HCT-8/5-FU, our aim was to search for highly efficient reversal agents and investigate the underlying mechanisms of this reversal. The cytotoxic effects of curcumin and 5-FU on HCT-8 and HCT-8/5-FU cells and the reversal effects of 5-FU in combination with curcumin on HCT-8/5-FU cells were measured using cell counting kit-8. Apoptosis and the cell cycle were analyzed by flow cytometry. Protein and mRNA expression levels of BCL-2, survivin, P-gp, and HSP-27 were detected by western blotting and quantitative real-time reverse transcription polymerase chain reaction, respectively. Curcumin inhibited the growth of HCT-8 and HCT-8/5-FU cells. It significantly reduced the IC50 of 5-FU for HCT-8/5-FU cells (P < 0.01) and the expression of BCL-2, survivin, P-gp, and HSP-27 in the cells. Curcumin can effectively reverse multidrug resistance in human colorectal cancer drug-resistant HCT-8/5-FU cells. The mechanism through which this occurs may be associated with decreased expression of BCL-2, survivin, P-gp, and HSP-27. Curcumin may therefore have clinical implications as a new agent for colorectal cancer.

The effect of curcumin on low-passage glioblastoma cells in vitro.

Plant extract therapy has been the cornerstone of cancer treatment for many years. The natural component curcumin demonstrated antineoplastic effects on different type of tumor cells. In this study, we explored the effectiveness of curcumin against low-passage human primary glioblastoma (GB) cell cultures. Early passage GB cell cultures (GB3B, GB4B, and GB5B) were established from fresh samples tissue obtained from GB patients. Growth rate (GR) and doubling time (DT) was determined for each cell line. The cytotoxic effect of curcumin was quantified by hemocytometer cell counting, using trypan blue. To study the changes in cell shape, GB cells exposed to a concentration corresponding to inhibitory concentration 50 (IC50) of curcumin were studied by phase-contrast microscopy by capturing images during the treatment. Our results showed that GB cells proliferate with a GR of 0.2872 and a DT of 2.41 days for GB3B, a GR of 0.2787 and a DT of 2.49 days for GB4B, and a GR of 0.2787 and a DT of 2.49 days for GB5B. Curcumin induced cell death in GB cells in a time- and dose-dependent manner. The IC50 for GB3B was 46.4 µM, for GB4B was 78,3 µM, and for GB5B was 47.7 µM. Phase contrast microscopy showed that cultures treated with curcumin in a concentration corresponding to IC50 contained rounded cells and cell fragments, 72 h after the treatment. The results of the present investigation proved that curcumin is a natural compound potentially useful in the fight against GB.

Curcumin inhibits the invasion of lung cancer cells by modulating the PKCα/Nox-2/ROS/ATF-2/MMP-9 signaling pathway.

Invasion and metastasis are the major causes of tumor-related mortality in lung cancer. It is believed that curcumin is an effective drug possessing anti-invasive and anti-metastatic activities in the treatment of cancer. However, the specific mechanisms remain unclear. In the present study, we investigated whether the PKCα/Nox-2/ATF-2/MMP-9 signaling pathway is involved in the invasive behavior of lung cancer and whether curcumin could inhibit invasion by modulating this pathway. The cytotoxic effect of curcumin was evaluated by MTT assay and the capacity of invasion was assessed by Transwell assay. siRNA and plasmid transfection techniques were used to study the function of targeted genes. Real-time PCR and western blot analysis were used to evaluate the expression levels of PKCα, Nox-2, MMP-9 and the phosphorylation of ATF-2. The results showed that curcumin inhibited the proliferation and invasion of A549 cells in a dose-dependent manner. Overexpression of MMP-9 enhanced the invasion of A549 cells. However, inhibition of MMP-9 by siRNA or curcumin suppressed cell invasion. Moreover, we also demonstrated the catalytic role of PKCα in expression of MMP-9 and cellular invasion in A549 cells, which was dependent on the expression of Nox-2 and phosphorylation of ATF-2. Finally, we also showed that curcumin dose-dependently reduced the expression of PKCα, P47phox, Nox-2 and phosphorylated ATF-2, as well as intracellular ROS generation, suggesting the inhibitory effect of curcumin on the activation of the PKCα/Nox-2/ROS/ATF-2 pathway. In conclusion, the PKCα/Nox-2/ROS/ATF-2/MMP-9 signaling pathway is activated in lung cancer A549 cells, which could be modulated by curcumin to inhibit cell invasiveness.

Curcumin Enhances the Radiosensitivity of U87 Cells by Inducing DUSP-2 Up-Regulation

Glioblastoma multiforme (GBM), an aggressive primary brain tumor, is radioresistant and recurs despite aggressive surgery, chemotherapy, and radiotherapy. Curcumin as a potential radiosensitizer has received extensive attention in cancer treatment. To explore an effectiveness of this radiosensitizer for GBM treatment, we evaluated the radiosensitizing effect of curcumin and investigated its potential molecular mechanisms in the human glioma cell line U87. The cytotoxic effects of curcumin on U87 cells were evaluated using the Cell Counting Kit-8 assay, and the radiosensitivity of U87 cells treated with curcumin was accessed by colony information assay. The effects of curcumin on cell proliferation and cell cycle regulation were determined using the 5-ethynyl-2-deoxyuridine incorporation assay and flow cytometry, respectively. Western blotting was applied to determine the effects of curcumin on protein expression of dual-specificity phosphatase-2 (DUSP-2), extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK) as well as phosphorylated ERK and JNK. Curcumin significantly inhibited the proliferation of U87 cells in a dose-and time-dependent manner. Curcumin treatment at the concentrations of 5 µM and 10 M could significantly reduce the clonogenic activity and enhance the radiosensitivity of U87 cells with sensitive enhancement ratios (SERs) of 1.71 and 4.65, respectively. Curcumin resulted in G2/M cell cycle arrest in U87 cells, which were radiosensitive. Pre-treatment of U87-MG cells with 5 µM curcumin enhanced radiation-induced cell proliferation inhibition and apoptosis. Furthermore, we observed that curcumin increased DUSP-2 protein expression and decreased the phosphorylation of ERK and JNK. Our results suggest that low-dose curcumin may enhance the radiosensitivity of human glioma U87 cells in vitro by inducing G2/M cell cycle arrest through up-regulation of DUSP-2 expression and inhibition of ERK and JNK phosphorylation.

GRP78 mediates the therapeutic efficacy of curcumin on colon cancer.

Glucose-regulated protein 78 (GRP78) is the key regulator of endoplasmic reticular (ER) function. Expression of GRP78 was correlated with malignancy in different cancers. However, the role of GRP78 in the cytotoxic effect of curcumin on colon cancer cells is still unclear. A silencing RNA (siRNA) technique was used to knock down GRP78 expression. The anticancer effects of curcumin were assessed by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, a flow cytometric cell cycle analysis, and a terminal dexynucleotidyl transferase-mediated nick end labeling (TUNEL) assay. HT-29 cells expressed lower GRP78 compared with DLD-1 cells. The MTT assay revealed that HT-29 cells were more resistant to curcumin treatment than DLD-1 cells. GRP78KD cells showed more resistance to curcumin treatment compared with scrambled control cells. Overexpressed GRP78 in HT-29 cells increased the sensitivity to curcumin treatment. According to the cell cycle analysis and TUNEL assay, we found that apoptosis dramatically increased in scrambled control cells compared to GRP78KD DLD-1 cells after curcumin treatment. Finally, we evaluated levels of Bcl-2, BAX, and Bad and found that an increase of Bcl-2 level was observed in GRP78KD cells treated with curcumin. Those results were consistent with the increasing of resistance to curcumin after silencing of GRP78. The levels of GRP78 expression might determine the therapeutic efficacy of curcumin against colon cancer cells.

Curcumin inhibits human retinal pigment epithelial cell proliferation.

Proliferative vitreoretinopathy (PVR) is a common cause of intraoperative failure following retinal reattachment surgery and is mediated in part through the migration, de-differentiation and proliferation of retinal pigment epithelial (RPE) cells. Given the cytotoxic effects of curcumin on epithelial and endothelial cells, in this study, we assessed the effects of curcumin on human RPE (hRPE) cell proliferation. WST-1 analysis revealed that curcumin significantly inhibited primary hRPE cell proliferation in a dose- and time-dependent manner (P<0.001) with the greatest inhibition observed at the dose of 15 μg/ml curcumin. Flow cytometric analysis indicated that the cytotoxic effects of curcumin on hRPE cell proliferation were mediated by cell cycle arrest at the G0/G1 phase and the induction of apoptosis (both P<0.001), which was confirmed by ultrastructural analysis using transmission electron microscopy. Furthermore, western blot analysis revealed that curcumin induced p53 and p21WAF1/CIP1 expression with a concomitant decrease in proliferating cell nuclear antigen protein levels (P<0.05). Curcumin effectively inhibited primary hRPE cell proliferation, which may be mediated by the p53 pathway. Further in vivo studies are required in order to fully explore the therapeutic potential of curcumin for PVR.

Curcumin inhibits leptin gene expression and secretion in breast cancer cells by estrogen receptors.

BackgroundRecent studies suggested that leptin as a mitogenic factor might play an important role in the process of initiation and progression of human cancer. Therefore, it could be considered as a target for breast cancer therapy. A previous study has showed that expression of leptin gene could be modulated by activation of estrogen receptors. Curcumin is a diferuloylmethane that has been shown to interfere with multiple cell signaling pathways and extensive research over the last 50 years has indicated this polyphenol can both prevent and treat cancer. Based on the fact that targeting of leptin could be considered as a novel strategy for breast cancer therapy, the aim of this study is the investigation of potentiality of curcumin for inhibition of leptin gene expression and secretion, and also, its link with expression of estrogen receptors.MethodsCytotoxic effect of curcumin on T47D breast cancer cells was investigated by MTT assay test after 24 and 48 treatments. Thereafter, the cells treated with different concentrations of curcumin. The levels of leptin, estrogen receptor α and estrogen receptor β genes expression was measured in the treated and control cells by Reverse-transcription real-time PCR. Amount of secreted leptin in the culture medium was also determined by ELISA in both treated and untreated cells. Finally data were statistically analyzed by one-way ANOVA test.ResultsAnalysis of MTT assay data showed that curcumin inhibits growth of T47D cells with dose dependent manner. There were also significant difference between control and treated cells in the levels of leptin, estrogen receptor α expression levels and the quantity of secreted leptin that both were decreased in the treated cells compared with control cells.ConclusionBased on the results, curcumin inhibits the expression and secretion of leptin and it could probably be used as a drug candidate for the breast cancer therapy through the leptin targeting in the future.