The protective effect of gallic acid against endocrine disrupting damages of Bisphenol A and possible mechanism

Abstract

Bekir Nihat Dogrul, Ibrahim Kiliccalan, Ekrem Samet Asci

Cancer is uncontrolled and/or abnormal cell growth and proliferation as a result of DNA damage. When the normal cells are exposed to DNA damage, they try to prevent this damage through various mechanisms. But in cancer, repair mechanisms of the cell are disrupted. Cells grow excessively and abnormally, and this threatens the life of organism. There are many factors that lead to carcinogenesis. One of these factors is endocrine disruptors. Endocrine disruptors can damage the body mechanisms to mimic certain hormones in the body. Bisphenol-A (BPA), which is one of the endocrine disrupting substances, is found in many products, such as plastic bottles, including primarily packaged foods. Exposure to BPA causes estrogen-mimetic feature which may lead to carcinogenesis through estrogen metabolism in cells. Phenolic compounds are widely present in plants which had beneficial effects on the body, and generally considered as health nutrients for human. We think, the phenolic compounds could have some positive effects on estrogen metabolism against BPA. To demonstrate that gallic acid (GA)—which is a prototype of phenolic compounds—, BPA and pure estrogen receptor blocker [fulvestrant (FV)] were applied to DU-145 (malign prostatic cancer cell) and HGF-1 (human gingival fibroblast cell) cell lines. FV was used to detect estrogen receptors related efficacy. We used 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) test to measure the cytotoxicity of chemical substances that we used. Effects of BPA and GA on estrogen metabolism were investigated by real-time polymerase chain reaction (PCR) method. In our study, MTT test showed that the GA decreased the cytotoxicity of BPA in cells. Using FV in combination with GA or BPA, also changed the percent of cell viability in MTT test, but these changes were negligible amount. Therefore, it could be considered that BPA and GA related effects are not only via estrogen receptor alpha and estrogen receptor beta. As a result of studies conducted by RT-PCR, we determined that GA and BPA had effects on enzymes of intracellular estrogen metabolism. FV caused changes on the effects of GA and BPA. This shows us that the these substances may show their effects via estrogen receptors. One of the most promising results of this study was: GA increased the expression of mRNA expression of glutathione S-transferase enzyme which increases detoxification and quinone reductase enzyme that decreases the DNA adducts. This showed us GA can also do protective effects to carcinogenic properties as well as endocrine disrupting effects of chemicals like BPA. GA also increased the expression of mRNA expression of poly (ADP-ribose) polymerase enzyme in benign cells, but not in malign cells specifically, which is an important step in DNA repair mechanism. We planned a new RT-PCR and Western Blot study in order to determine the possible role of estrogen receptors and estrogen metabolism related enzymes in the mechanism of the preventive effect of phenolic compounds against endocrine disrupters more precisely, in over cancer, mammary cancer and prostate cancer cell lines, and we believed that this would be very informative for the understanding the underlying mechanism of endocrine disrupters and cancer.