October 9 - 12, 2012
Building 10 & Natcher Conference Center
- General Schedule of Events
- Opening Plenary Session
- Concurrent Symposia Sessions
- Poster Sessions
- National Graduate Student Research Conference
- FARE Award Ceremony
- Special Exhibits on Resources for Intramural Research
- TSA Research Festival Exhibit Show
- Clinical Center Tours
- Research Festival Committees
- Past Research Festivals
The effect of mitochondrially-targeted compounds mitoquinone and mitotempol on genomic DNA integrity and the potential impact on cell survival
| Thursday, November 07, 2013 — Poster Session II | |||
|---|---|---|---|
12:00 p.m. – 2:00 p.m. |
FAES Academic Center (Upper-Level Terrace) |
FDA/CBER |
CHEMCELL-4 |
Authors
- TA Denison
- VA Rao
Abstract
The triphenylphosphonium compounds mitoquinone (mitoQ) and mitotempol (mitoT) were designed as mitochondrially-targeted antioxidants to mitigate oxidative damage in cells. However, we and others have shown that mitoQ increases superoxide and reduces tumor viability in cells and in animal models. MitoQ was particularly cytotoxic to breast cancer cells versus normal breast cells, and was shown to increase autophagy along with apoptotic cell death. The varied effects of these compounds may stem from complex and multiple mechanisms related to their redox cycling in the mitochondria. One aspect not fully understood is mitochondrially-targeted compounds may directly or indirectly affect genomic DNA damage within the cell, and how any such damage might mediate survival mechanisms. Western blotting revealed that mitoQ treatment increased levels of phosphorylated H2AX (gH2AX) histone, a known marker for DNA double-stranded breaks, by 24 hours at both 1 μM and 5 μM concentrations. MitoT had a faster affect showing increased H2AX levels as early as 1 hr for 5 μM, and by 6 hours for 1 μM. We will present our findings on the nature and potential mechanisms of oxidative DNA damage following exposure of cancer cells to redox active mitoQ and mitoT.
