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 Kachhap, Channing Paller, Janet Mendonca, Leo Li-Ying Chan, Bo Lin, Diane K. Hartle, Jeffrey E. Green, Collis A. Brown, Tamaro S. Hudson

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article numbere01128
JournalHeliyon
Volume5
Issue number1
DOIs
StatePublished - Jan 1 2019

Keywords

  • Cancer research
  • Cell biology
  • Molecular biology

ASJC Scopus subject areas

  • General

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    Ignacio, D. N., Mason, K. D., Hackett-Morton, E. C., Albanese, C., Ringer, L., Wagner, W. D., Wang, P. C., Carducci, M. A., Kachhap, S., Paller, C., Mendonca, J., Li-Ying Chan, L., Lin, B., Hartle, D. K., Green, J. E., Brown, C. A., & Hudson, T. S. (2019). Muscadine grape skin extract inhibits prostate cancer cells by inducing cell-cycle arrest, and decreasing migration through heat shock protein 40. Heliyon, 5(1), [e01128]. https://doi.org/10.1016/j.heliyon.2019.e01128