Accession Number:

ADA564586

Title:

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

Descriptive Note:

Annual rept. 1 Mar 2010-29 Feb 2012

Corporate Author:

OREGON HEALTH AND SCIENCE UNIV PORTLAND

Personal Author(s):

• Qian, David

Report Date:

2012-03-01

Pagination or Media Count:

8.0

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.

Descriptors:

• *CHEMOTHERAPY
• *MITOCHONDRIA
• *PROSTATE CANCER
• CLINICAL MEDICINE
• ENZYMES
• METABOLISM
• MOLECULES
• PROSTATE GLAND

Subject Categories:

• Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE