Abstract B70: Thymoquinone regulates cytochrome P450 genes involved in prostate cancer disparity

Abstract

African American (AA) men have a higher incidence and greater mortality from prostate cancer (PCa) than Caucasian American (CA) men. The factor influencing the racial disparity is not clearly understood and is probably genetic variation attributed to the disease. Androgen and androgen receptor (AR) pathways have long been associated with prostate growth. Racial differences have also been found among variants of the genes of the enzymes involved in androgen biosynthesis and metabolism, such as CYP3A4, CYP3A7, and CYP17A1. Although several inhibitors are approved for CYPs genes, the major drawback of these inhibitors is they contain the steroid scaffold, which contributes to the undesirable side effects (dyspnea, edema, contusion, etc.) observed in patients. In this regard, using nonsteroid scaffolds such as natural compound acts as a more potent inhibitor and interacts more selectively with the cytochrome P450 family. In this study, our data showed the effect of natural compound thymoquinone (TQ), a constituent of Nigella sativa (black seed), on CYP3A4, CYP3A7, and CYP17A1 genes in PCa cells, and found that TQ-treated cells significantly downregulated the expression of CYP3A4, CYP3A7, and CYP17A1 in MDA PCa 2b and E006AA-hT (African American) compared to LNCaP (Caucasian) cell lines. These findings were further confirmed by flow cytometry, Western blots, and immunofluorescence. These studies suggested that TQ could be the potent inhibitor of the active sites of the cytochrome P450 enzymes, which are an important target in the treatment of PCa. Additionally, knowledge of the PCa susceptibility genes (CYPs) could be used to identify individuals at risk of developing PCa with poor outcomes for heightened screening or prevention modalities and to identify optimal treatment strategies for men of African descent. Citation Format: Santosh K. Singh, James W. Lillard, Jr., Rajesh Singh. Thymoquinone regulates cytochrome P450 genes involved in prostate cancer disparity [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr B70.