Muscadine grape skin extract inhibits prostate cancer cells by inducing cell-cycle arrest, and decreasing migration through heat shock protein 40

Diane N. Ignacio ? Kimberly D. Mason ? Ezra C. Hackett-Morton ? Christopher Albanese ? Lymor Ringer ? William D. Wagner ? Paul C. Wang ? Michael A. Carducci? Sushant K. Kachhap ? Channing J. Paller ? Janet Mendonca ? Leo Li-Ying Chan ? Bo Lin ? Diane K. Hartle ? Jeffrey E. Green ? Collis A. Brown ? Tamaro S. Hudson

Diane Ignacio

e01128January 2019

Heliyon

2019

JANUARY

1

5

Cancer research Cell biology Molecular biology

Previously we demonstrated that muscadine grape skin extract (MSKE), a natural product, significantly inhibited androgen-responsive prostate cancer cell growth by inducing apoptosis through the targeting of survival pathways. However, the therapeutic effect of MSKE on more aggressive androgen-independent prostate cancer remains unknown. This study examined the effects of MSKE treatment in metastatic prostate cancer using complementary PC-3 cells and xenograft model. 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 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 demonstrate that MSKE significantly inhibited cell migration in PC-3 prostate cancer cells. 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 either as a neo-adjuvant or therapeutic for castration resistant prostate cancer.

Completed

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