MUSCADINE GRAPE SKIN EXTRACT INHIBITS ANDROGEN‐INDEPENDENT PROSTATE CANCER CELL GROWTH, INDUCING CELL‐CYCLE ARREST, AND DECREASING MIGRATION BY TARGETING HEAT SHOCK PROTEIN 40

Abstract

Previously we demonstrated that muscadine grape skin extract (MSKE), a natural product, significantly inhibited prostate cancer cell growth by inducing apoptosis through the targeting of phosphatidylinositol 3‐kinase‐Akt and mitogen‐activated protein kinase survival pathways in androgen‐responsive transformed human prostate cancer epithelial cell lines. However, the preventive effect of MSKE on more aggressive androgen‐independent prostate cancer remains unknown. This study examined the effects of MSKE treatment using complementary PC‐3 prostate cancer cell culture and xenograft models. MSKE significantly inhibited PC‐3 human prostate cancer cell tumor growth in vitro and in vivo. The growth‐inhibitory effect of MSKE appeared to be through the induction of cell‐cycle arrest. This induction was accompanied by a reduction in the protein expression of Hsp40 protein and cell‐cycle regulation proteins, cyclin D1 and NF‐kBp65. In addition, MSKE induced p21 expression independent of wild‐type p53 induced protein expression. Moreover, we demonstrated that MSKE significantly inhibited cell migration in PC‐3 prostate cancer cells which was complimented by siRNA‐HSP40 knock‐down that also inhibited cell migration and growth. Overall, these results demonstrate that MSKE inhibits prostate tumor growth and migration, and induces cell‐cycle arrest by targeting Hsp40 and proteins involved in cell‐cycle regulation and proliferation. This suggests that MSKE may also be explored as a novel therapeutic in castration resistant prostate cancer.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.