The Role of Mitochondrial TCA Cycle Enzymes in Determining Prostate Cancer Chemosensitivity

Abstract

Based on the results in preliminary data and in year #1 of the proposal, we hypothesize that MDH2 plays a crucial role in determining prostate cancer chemosensitivity. In year #2, we further determined the effect of inhibiting MDH2 on prostate cancer energy metabolism and response to chemotherapy. We found that MDH2 knockdown via stable shRNA significantly disrupts the metabolic efficiency and redox balance in prostate cancer cells. Further, we made a novel observation that MDH2 knockdown significantly enhances the chemotherapy induced signaling cascade that is required to exert mitochondria-based apoptosis. This provides a potential mechanism underpinning the observed clinical correlation between MDH2 and outcome of chemotherapy in prostate cancer. It also presents evidence for the first time that MDH2 can be a novel molecular target to improve prostate cancer chemotherapy.

Open PDF

Document Details

Document Type
Technical Report
Publication Date
Mar 01, 2012
Accession Number
ADA564586

Entities

People

  • David Qian

Organizations

  • Oregon Health & Science University

Tags

Communities of Interest

  • Biomedical

DTIC Thesaurus Topics

  • Apoptosis
  • Biological Sciences
  • Biomedical Research
  • Cell Line
  • Cells
  • Chemotherapy
  • Cultured Cells
  • Instructions
  • Metabolic Pathways
  • Metabolism
  • Metabolites
  • Mitochondria
  • Neoplasms
  • Peak Values
  • Phosphorylation
  • Prostate
  • Prostate Cancer

Fields of Study

  • Chemistry
  • Medicine

Readers

  • Cardiovascular Physiology
  • Molecular and Cellular Biology
  • Women's Health and Cancer Risk Research: African American Women and Pregnancy Outcomes.