TITLE:
Microdoses Levels of Butadiene Diepoxide (BDO2) Induced Toxicity in Prostate Cancer Cells
AUTHORS:
Sowmya Koppula, Mei-Chyi Tan, Angela Hurst, Caroline Telles, Wesley Gray
KEYWORDS:
BDO2; Cytotoxicity; Gene Expression; Prostate; Micro-Dose
JOURNAL NAME:
Pharmacology & Pharmacy,
Vol.4 No.2,
April
15,
2013
ABSTRACT: Low-level exposure to environmental pollutants such as BDO2 contributes directly and indirectly to an increase in PCa. The aim of this study was to define the cellular changes associated with micro-doses of Butadiene Diepoxide (BDO2) in prostate cancer cells. We observed that micro-doses of BDO2 resulted in dose- and time-dependent increases in cytotoxicity and increased expression of prostate tumor markers in LNCaP(AR+) and DU145(AR-) cells. There was an increased sensitivity of DU145(AR-) cells to BDO2 toxicity which was reversed by transient transfection of AR into theses cell. Exposure of prostate cells to BDO2 increases cytotoxicity, and apoptosis, which correlates with increases in caspases and Bcl2 protein and mRNA levels. In cell DU145(AR-) cell transient transfected with a functional AR, the levels of cytotoxicity and caspase activity were decreased in the presence of BDO2, but BDO2-induced apoptotic protein expression was unaltered. This study provides evidence that micro-doses of BDO2 modulate prostate cell toxicity by promoting apoptosis and tumor gene expression.