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
Affiliations
Diane N. Ignacio
Howard University Cancer Center, Washington DC 20060, United States; The University of the West Indies, St. Augustine Campus, Faculty of Medical Sciences, School of Pharmacy, Eric Williams Medical Sciences Complex, Champs Fleurs, Trinidad and Tobago
Kimberly D. Mason
Howard University Cancer Center, Washington DC 20060, United States
Ezra C. Hackett-Morton
Howard University Cancer Center, Washington DC 20060, United States
Christopher Albanese
Lombardi Cancer Center, Georgetown University Medical Center, Washington DC, United States
Lymor Ringer
Lombardi Cancer Center, Georgetown University Medical Center, Washington DC, United States
William D. Wagner
Department of Plastic and Reconstructive Surgery, Wake Forest University School of Medicine, Winston Salem, NC 27157, United States
Paul C. Wang
Howard University Cancer Center, Washington DC 20060, United States; College of Science and Engineering, Fu Jen Catholic University, New Taipei City, Taiwan
Michael A. Carducci
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States
Sushant K. Kachhap
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States
Channing J. Paller
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States
Janet Mendonca
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States
Leo Li-Ying Chan
Department of Technology R&D, Nexcelom Bioscience LLC, Lawrence, MA 01843, United States
Bo Lin
Department of Technology R&D, Nexcelom Bioscience LLC, Lawrence, MA 01843, United States
Diane K. Hartle
Department of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, GA 30602, United States
Jeffrey E. Green
Laboratory of Cell Biology and Genetics, National Cancer Institute, NIH, Bethesda, MD 20892, United States
Collis A. Brown
Howard University Cancer Center, Washington DC 20060, United States; Department of Pharmacology, Howard University College of Medicine, Washington DC 20059, United States
Tamaro S. Hudson
Howard University Cancer Center, Washington DC 20060, United States; Department of Pharmacology, Howard University College of Medicine, Washington DC 20059, United States; Department of Research, Washington VA Medical Center, Washington DC, United States; Corresponding author.
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.
