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Author Notes:

Correspondence: Valerie A Odero-Marah; vodero_marah@cau.edu

Authors’ contributions: LB and PB contributed equally.

LB performed experiments, analyzed data and generated figures and manuscript.

PB performed experiments, analyzed data and generated figures and manuscript.

RSA conducted DHE studies.

KK synthesized and provided the HydroCy3 dye.

NM synthesized and provided the HydroCy3 dye.

VOM designed project, project coordination, and manuscript preparation.

All authors have read and approved the final version of the manuscript.

Disclosures: The authors declare that they have no competing interest.

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Research Funding:

This project was supported by grants from the National Institutes of Health. NIH/NIMHD/RCMI Grant #8 G12 MD007590 and NIH/NIMHD/P20 Grant #2 P20 MD002285. Grant supported by: NIH grants 1P20MD002285 (VOM), G12RR03062 (VOM).

Keywords:

  • Muscadine grape skin extract
  • Snail
  • EMT
  • Reactive oxygen species
  • Superoxide
  • Prostate cancer

Muscadine grape skin extract reverts snail-mediated epithelial mesenchymal transition via superoxide species in human prostate cancer cells

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Journal Title:

BMC Complementary and Alternative Medicine

Volume:

Volume 14, Number 97

Publisher:

Type of Work:

Article | Final Publisher PDF

Abstract:

Background Snail transcription factor can induce epithelial-mesenchymal transition (EMT), associated with decreased cell adhesion-associated molecules like E-cadherin, increased mesenchymal markers like vimentin, leading to increased motility, invasion and metastasis. Muscadine grape skin extract (MSKE) has been shown to inhibit prostate cancer cell growth and induce apoptosis without affecting normal prostate epithelial cells. We investigated novel molecular mechanisms by which Snail promotes EMT in prostate cancer cells via Reactive Oxygen Species (ROS) and whether it can be antagonized by MSKE. Methods ARCaP and LNCaP cells overexpressing Snail were utilized to examine levels of reactive oxygen species (ROS), specifically, superoxide, in vitro using Dihydroethidium (DHE) or HydroCy3 dyes. Mitosox staining was performed to determine whether the source of ROS was mitochondrial in origin. We also investigated the effect of Muscadine grape skin extract (MSKE) on EMT marker expression by western blot analysis. Migration and cell viability using MTS proliferation assay was performed following MSKE treatments. Results Snail overexpression in ARCaP and LNCaP cells was associated with increased concentration of mitochondrial superoxide, in vitro. Interestingly, MSKE decreased superoxide levels in ARCaP and LNCaP cells. Additionally, MSKE and Superoxide Dismutase (SOD) reverted EMT as evidenced by decreased vimentin levels and re-induction of E-cadherin expression in ARCaP-Snail cells after 3 days, concomitant with reduced cell migration. MSKE also decreased Stat-3 activity in ARCaP-Snail cells. Conclusions This study shows that superoxide species may play a role in Snail transcription factor-mediated EMT. Therefore, therapeutic targeting of Snail with various antioxidants such as MSKE may prove beneficial in abrogating EMT and ROS-mediated tumor progression in human prostate cancer.

Copyright information:

doi:10.1186/1472-6882-14-97

This is an Open Access work distributed under the terms of the Creative Commons Attribution 2.0 Generic License (http://creativecommons.org/licenses/by/2.0/).

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