Chemoprotective potential of DIM (3,3 '-Di-indolyl-methane) and Genistein in LNCaP and PC-3 human prostate cancer cells exposed to Bisphenol A

Abstract

The prostate cancer presents hormonal basis for their initiation and progression of events and these are mainly related to changes involving estrogens and androgens inherent aging process, where there is an increase of androgens relative to estrogens. Nowadays, bisphenol A (BPA) is the most studied xenoestrogen and its estrogenic activity has attracted attention for its wide dispersion in the environment. Thus, this compound could contribute to the increased incidence, aggressiveness and metastatic ability of prostate tumors. Moreover, the chemoprotection with dietary phytochemicals associated with a reduction in the incidence and progression of different cancers, decrease inflammatory processes and oxidative stress caused by potentially harmful substances. Thus, this study aims to evaluate the effects of phytochemicals 3,3 '-Di-indolyl-methane (DIM) and Genistein (Gen) isolated and/or associated to prostatic tumor cells exposed to BPA. For this purpose, LNCaP prostate tumor cells and PC-3 are cultured in a specific pattern (MC) to expand until they reach 80% confluency. Then, they will be trypsinized and transferred to 6-well plates and subjected to the treatments: T1: MC; T2: MC+BPA; T3: MC+BPA+DIM; T4: MC+BPA+Gen; T5: MC+BPA+DIM+Gen; for 96 hours. The doses of the chemical will be identified by viability assay and determination of the IC50. The viability and migration speed of tumor cells against exposure to bisphenol A and after addition of DIM and Genistein isolated and / or associated will be evaluated. Additionally, cells are subjected to protein extraction for Western Blotting in order to analyze proteins: Akt, MAPK, BCL2 and BAX (proliferation and cell death); AR, ER±, ER² (survival and hormonal modulation) and SIRT1 (oxidative stress and metastatic potential). The results may contribute for understanding the response of tumor cells exposed to environmental BPA xenoestrogen and modulating effects of phytochemicals on this response.