Genomic Instability, Epigenetics and Metabolism
Colleges & Departments:
College of Medicine, Department of Toxicology and Cancer Biology
My research interests are centered on role(s) of redox state and cancer progression, particularly, subcellular redox states. Elucidating the molecular mechanisms underlying redox state-regulated gene/protein expression is critical for understanding behavior of cancer cells. Previously, we discovered that both intra- and extracellular redox states were significantly different between prostate cancer cells and normal prostate epithelial cells; intracellular redox state become more oxidized while extracellular redox state become more reduced in prostate cancer cell lines. These differences correlated with prostate cancer cell growth and invasion. Additionally, alteration of extracellular redox state by overexpression of extracellular superoxide dismutase (ECSOD) or decreasing of extracellular spaces redox potential values through varying cysteine/cystine ratio significantly inhibited prostate cancer invasion, whereas alteration of intracellular redox state by overexpression of manganese superoxide dismutase (MnSOD) or treatment with glutathione-depleting compounds significantly inhibited cell growth. Currently, we investigate the expression levels of selected antioxidant proteins (e.g. MnSOD, thioredoxin 1, or ECSOD) at specific subcellular organelle in epithelial vs. stromal cells of benign vs. cancer tissues of prostate cancer patients using immunohistochemistry staining with specific antibodies and Aperio Image analysis system. The study is the first to focus on site-specific intra- and extracellular redox imbalances as new therapeutic target proteins for prostate cancer treatment. Another important and exciting aspect of my current work is using cutting edge tool, nitroxides-enhanced MRI to measure tissue redox activity in prostate cancer of living mice. The assay is based on nitroxides redox cycling coupled with appearance/disappearance of an enhanced MRI signal, which make them useful molecular sensors for changing redox state. This method may be used as a tool for diagnosis and therapy guidance since it has low toxicity, minimal side effects, and has a short half-life for imaging. In summary, differences in tissue redox activities and antioxidant protein levels may serve as biomarkers to identify cancer from non-cancer in prostate biopsies and identify patients with low grade cancers who will progress to high grade cancers, providing possible new information to guide therapeutic decisions.
- Increasing discordant antioxidant protein levels and enzymatic activities contribute to increasing redox imbalance observed during human prostate cancer progression. Chaiswing L, Zhong W, Oberley TD. Free Radic Biol Med, 67:342-52, 2014. PMCID: PMC3945156.
- RelB is a central regulator that adjudicates the differential effects of ascorbic acid in normal and cancer cells. Wei X, Xu Y, Xu F, Chaiswing L, Schnell D, Noel T, Wang C, Chen J, St. Clair DK, and St. Clair WH. Cancer Res, Epub ahead of print, 2017.
- Regulation of prostate cancer cell invasion by modulation of extra- and intracellular redox balance. Chaiswing L, Zhong W, Liang Y, Jones DP, Oberley TD. Free Radic Biol Med 52:452-61, 2012. PMCID: PMC3253260.
- Extracellular/microenvironmental redox state. Chaiswing L and Oberley TD. Antioxid Redox Signal 13:449-65, 2010.