Original articleEpigallocatechin-3-gallate promotes apoptosis in human breast cancer T47D cells through down-regulation of PI3K/AKT and Telomerase
Introduction
The most common cancer among women is breast cancer (17.1 per 100,000 person-year), which has mainly affected Iranian women about a decade earlier than western countries [1], [2]. Presently, common treatments for breast cancer are chemotherapy, radiotherapy and surgery. Current systemic therapies for breast cancer are often limited by major organ damage, short-term efficacy due to the emergence of drug resistance and poor prognosis [3]. So, the search for new antitumor agent’s development with improved efficacy and side-effect profile has been continued. Researchers believe that dietary phytochemical agents may influence chemotherapy treatment and help cure patients with cancer. Different natural compounds can improve the efficiency of chemotherapeutic agents, decrease resistance of chemotherapeutic drugs, and lower as well as alleviate adverse side-effects of chemotherapy [4]. As a result, researchers attempt to employ different herbs and their effective agents both in vitro and in vivo for cancer therapy. Most herbs contain antioxidant agents that could be consumed to prevent cancer or potentiate chemotherapy. Experimentally, several medicinal plants and herbal ingredients have been reported to have anticancer effects [5]. Also, a number of phytochemicals isolated from medicinal plants have been shown to decrease cell proliferation, induce apoptosis, retard metastasis and inhibit angiogenesis [6]. Currently, some of these plant-derived compounds are widely used for the chemotherapy of patients with cancer. For example, taxol analogues, vinca alkaloids (vincristine, vinblastine), and podophyllotoxin analogues have played an important role in the treatment of such patients [7]. Green tea is a popular beverage in Asia. Epidemiological studies have suggested that drinking green tea is effective in the treatment of different diseases. Based on many in vivo and in vitro studies, the biological activity of green tea is mediated by its major polyphenolic constituent, epigallocatechin gallate (EGCG), which is a potent antioxidant [8]. The beneficial effects of EGCG are reported in the treatment of cancer, cardiovascular diseases, diabetes, neurodegenerative diseases, and liver diseases. It reduces the risk of cancer developing in the prostate, bladder, stomach, oesophagus and lung [9], [10], [11], [12], [13]. In the pioneer study confirmed that EGCG affected the ERα-positive cells more than ERα-negative breast cancer cells [14]. Therefore, we chose T47D cells (as estrogen receptor α-positive breast cancer cell model) to evaluate the effects of EGCG on proliferation and apoptosis compared with tamoxifen (as positive control). It was also aimed to determine whether antitumor effects of EGCG are associated with altering of PI3K/AKT and telomerase genes expressions.
Section snippets
Cell lines and reagents
The estrogen receptor positive human breast cancer cell line T47D and normal Human Foreskin Fibroblast cell line HFF were obtained from Pasteur Institute of Iran. Dulbecco’s Modified Eagle’s Medium (DMEM), fetal bovine serum, trypsin, penicillin and streptomycin were obtained from Gibco BRL Life Technologies (USA). The 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium (MTT) 4-, OH-tamoxifen and EGCG (>95%) were purchased from Sigma-Aldrich company (USA). Tripure was purchased from
EGCG decreased cell viability in a concentration-dependent manner
T47D and HFF cell lines were treated with different concentrations of EGCG (10–80 μM) or tamoxifen (2.5–20 μM) for up to 72 h. Then, cell viability was measured by MTT assay. Exposure to EGCG or tamoxifen showed concentration-dependent suppression in cell survival (Fig. 1A). The toxicity of EGCG and tamoxifen was significantly higher in T47D than HFF cells. The results are summarized in Table 2.
The IC50 (concentration of 50% inhibition) values of EGCG in T47D cells were 46.88, 22.31 and 14.17 μM at
Discussion
Breast cancer is the most common cancer and, after lung cancer, is the second cause of cancer death in women. Defects in the apoptotic pathways are responsible for both the disease pathogenesis and its therapy resistance. It is thus a good candidate for treatment by pro-apoptotic agents [1]. Natural products have long been utilized to prevent and treat neoplasms; therefore, searching for natural products directed at the inducing apoptosis of cancer cells may be a great strategy for breast
Funding
This work was supported by a grant from the Vice Chancellor for Research and Technology, Jahrom University of Medical Sciences, Jahrom, Iran.
Authors and contributions
Design study and collection data: M.M.; Analysis and interpretation of data: S.E., H.R.; Writing of manuscript and decision to submit the article for publication: A.H., M.M.
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