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

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HSP40 Heat-Shock Proteins
Vitis
Cell Cycle Checkpoints
Prostatic Neoplasms
Skin
Growth
Androgens
Cell Cycle Proteins
Castration
Cyclin D1
Therapeutic Uses
Protein Transport
Biological Products
Heterografts
Cell Movement
Prostate
Neoplasms
Cell Cycle
Proteins
Cell Proliferation

Keywords

  • Cancer research
  • Cell biology
  • Molecular biology

ASJC Scopus subject areas

  • General

Cite this

Ignacio, D. N., Mason, K. D., Hackett-Morton, E. C., Albanese, C., Ringer, L., Wagner, W. D., ... 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

Muscadine grape skin extract inhibits prostate cancer cells by inducing cell-cycle arrest, and decreasing migration through heat shock protein 40. / Ignacio, Diane N.; Mason, Kimberly D.; Hackett-Morton, Ezra C.; Albanese, Christopher; Ringer, Lymor; Wagner, William D.; Wang, Paul C.; Carducci, Michael A; Kachhap, Sushant; Paller, Channing; Mendonca, Janet; Li-Ying Chan, Leo; Lin, Bo; Hartle, Diane K.; Green, Jeffrey E.; Brown, Collis A.; Hudson, Tamaro S.

In: Heliyon, Vol. 5, No. 1, e01128, 01.01.2019.

Research output: Contribution to journalArticle

Ignacio, DN, Mason, KD, Hackett-Morton, EC, Albanese, C, Ringer, L, Wagner, WD, Wang, PC, Carducci, MA, Kachhap, S, Paller, C, Mendonca, J, Li-Ying Chan, L, Lin, B, Hartle, DK, Green, JE, Brown, CA & Hudson, TS 2019, 'Muscadine grape skin extract inhibits prostate cancer cells by inducing cell-cycle arrest, and decreasing migration through heat shock protein 40', Heliyon, vol. 5, no. 1, e01128. https://doi.org/10.1016/j.heliyon.2019.e01128
Ignacio, Diane N. ; Mason, Kimberly D. ; Hackett-Morton, Ezra C. ; Albanese, Christopher ; Ringer, Lymor ; Wagner, William D. ; Wang, Paul C. ; Carducci, Michael A ; Kachhap, Sushant ; Paller, Channing ; Mendonca, Janet ; Li-Ying Chan, Leo ; Lin, Bo ; Hartle, Diane K. ; Green, Jeffrey E. ; Brown, Collis A. ; Hudson, Tamaro S. / Muscadine grape skin extract inhibits prostate cancer cells by inducing cell-cycle arrest, and decreasing migration through heat shock protein 40. In: Heliyon. 2019 ; Vol. 5, No. 1.
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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.",
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AU - Ringer, Lymor

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AU - Wang, Paul C.

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AU - Mendonca, Janet

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AU - Lin, Bo

AU - Hartle, Diane K.

AU - Green, Jeffrey E.

AU - Brown, Collis A.

AU - Hudson, Tamaro S.

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