Resveratrol downregulates KIF15 in prostate cancer cells

Abstract

Kinesin family member 15 (KIF15) is best known as a stabilizer for bipolar spindle formation during cell division. By interacting with the actin cytoskeleton, KIF15 is also involved in cell proliferation, apoptosis, and differentiation, and therefore implicated in several types of malignancies including liver, pancreatic, and breast cancers. In castration-resistant prostate cancer cells, KIF15 protects AR/AR-V7 from degradation by binding the N-terminus of AR/AR-V7 and enhancing the recruitment of deubiquitinating enzyme ubiquitin-specific protease 14 (USP14). On the other hand, KIF15 is upregulated by AR transcriptionally. We have previously reported that resveratrol (RSV) downregulates ARV7 in prostate cancer cells by enhancing ubiquitination-mediated ARV7 degradation. To understand if KIF15 plays a role in RSV-mediated ARV7 degradation, we treated 22RV1, an ARV7-positive cell line, with RSV and estimated the levels of KIF15 by Western blot assays. We found that RSV downregulates KIF15 in a dose (20uM-100uM) and time (24 or 48h)-dependent manner. Intriguingly, we also noticed some morphological changes when the cells were treated with RSV. Next, we will test if RSV-mediated ARV7 downregulation is KIF15-dependent. If so, we will explore whether RSV and KIF15 inhibitor inhibit RSV-positive prostate cancer cell proliferation additively or synergistically. We will also treat both 22RV1 and WPMY-1 cells (a normal prostate cell line) with RSV to see if RSV’s effect on morphological change is cancer cell-specific

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