- 452 HSRB Bosomworth
- Lexington KY
Ph.D, Mahidol University, Thailand
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.
1. Zhao Y, Oberley TD, Chaiswing L, Lin SM, Epstein CJ, Huang TT, St Clair D: Manganese superoxide dismutase deficiency enhances cell turnover via tumor promoter-induced alterations in AP-1 and p53-mediated pathways in a skin cancer model. Oncogene 2002, May 30;21(24):3836-46.
2. Chaiswing L, Cole MP, St Clair DK, Ittarat W, Szweda LI, Oberley TD: Oxidative damage precedes nitrative damage in adriamycin-induced cardiac mitochondrial injury. Toxicol Pathol 2004, Sep-Oct;32(5):536-47.
3. Chaiswing L, Cole MP, Ittarat W, Szweda LI, St Clair DK, Oberley TD: Manganese superoxide dismutase and inducible nitric oxide synthase modify early oxidative events in acute adriamycin-induced mitochondrial toxicity. Mol Cancer Ther 2005, Jul;4(7):1056-64.
4. Li Y, Wheeler DL, Alters W, Chaiswing L, Verma AK, Oberley TD: Early epidermal destruction with subsequent epidermal hyperplasia is a unique feature of the papilloma-independent squamous cell carcinoma phenotype in PKC epsilon overexpressing transgenic mice. Toxicol Pathol 2005, 33(6):684-94.
5. Zhao Y, Chaiswing L, Oberley TD, Batinic-Haberle I, St Clair W, Epstein CJ, St Clair D: A mechanism based antioxidant approach for the reduction of skin carcinogenesis. Cancer Res 2005, Feb 15;65(4):1401-5.
6. Zhao Y, Chaiswing L, Velez JM, Batinic-Haberle I, Colburn NH, Oberley TD, St Clair DK: p53 translocation to mitochondria precedes its nuclear translocation and targets mitochondrial oxidative defense protein-manganese superoxide dismutase. Cancer Res 2005, May 1;65(9):3745-50.
7. Cole MP, Chaiswing L, Oberley TD, Edelmann SE, Piascik MT, Lin SM, Kiningham KK, St Clair DK: The protective roles of nitric oxide and superoxide dismutase in adriamycin-induced cardiotoxicity. Cardiovasc Res 2006, Jan;69(1):186-97.
8. Zhao Y, Wang LM, Chaiswing L, Yen HC, Oberley TD, Lien YC, Lin SM, Mattson MP, St Clair DK: Tamoxifen protects against acute tumor necrosis factor alpha-induced cardiac injury via improving mitochondrial functions. Free Radic Biol Med 2006, Apr 1;40(7):1234-41.
9. Zhao Y, Chaiswing L, Bakthavatchalu V, Oberley TD, St Clair DK: Ras mutation promotes p53 activation and apoptosis of skin keratinocytes. Carcinogenesis 2006, Aug 27(8):1692-8.
10. Chaiswing L, Bourdeau-Heller JM, Zhong W, Oberley TD: Characterization of redox state of two human prostate carcinoma cell lines with different degrees of aggressiveness. Free Radic Biol Med 2007, Jul 15;43(2):202-15.
11. Chaiswing L, Zhong W, Cullen JJ, Oberley LW, Oberley TD: Extracellular redox state regulates features associated with prostate cancer cell invasion. Cancer Res2008, Jul 15;68(14):5820-6.
12. Dhar SK, Tangpong J, Chaiswing L, Oberley TD, St Clair DK: Manganese superoxide dismutase is a p53- regulated gene that switches cancers between early and advanced stages. Cancer Res 2011, 71: 6684-95.
13. Chaiswing L, Zhong W, Oberley TD: Distinct Redox Profiles of Selected Human Prostate Carcinoma Cell Lines: Implications for Rational Design of Redox Therapy. Cancers 2011, 3(3): 3557-3584.
14. Chaiswing L, Zhong W, Liang Y, Jones DP, Oberley TD: Regulation of prostate cancer cell invasion by modulation of extra- and intracellular redox balance. Free Radic Biol Med 2012, 52: 452-61.
15. Xu Y, Fang F, Miriyala S, Crooks PA, Oberley TD, Chaiswing L, Noel T, Holley AK, Zhao Y, Kiningham KK, St Clair DK, St Clair WH. KEAP1 Is a Redox Sensitive Target That Arbitrates the Opposing Radiosensitive Effects of Parthenolide in Normal and Cancer Cells. Cancer Res. 2013 Jul 15;73(14):4406-17.
16. Cole MP, Tangpong J, Oberley TD, Chaiswing L, Kiningham KK, St Clair DK. Nuclear Interaction between ADR-Induced p65 and p53 Mediates Cardiac Injury in iNOS (-/-) Mice. PLoS One. 2014 Feb 25;9(2):e89251.
17. Chaiswing L, Zhong W, Oberley TD. Increasingly discordant antioxidant protein levels and enzymatic activities contribute to redox imbalance observed during human prostate cancer progression. Free Radic Biol Med. 2014 Feb;67:342-52
18. Deng J, Coy D, Zhang W, Sunkara M, Morris AJ, Wang C, Chaiswing L, St Clair D, Vore M, Jungsuwadee P. Elevated glutathione is insufficient to protect against doxorubicin-induced nuclear damage in heart in multidrug resistance associated protein 1 (Mrp1/Abcc1) null mice. J Pharmacol Exp Ther. 355(2):272-279, 2015 Sep 9.
19. Miriyala S, Thippakorn C, Chaiswing L, Xu Y, Noel T, Tovmasyan A, Batinic-Haberle I, Vander Kooi CW, Chi W, Latif AA, Panchatcharam M, Prachayasittikul V, Allan Butterfield D, Vore M, Moscow J, St Clair DK. Novel role of 4-hydroxy-2-nonenal in AIFm2-mediated mitochondrial stress signaling. Free Radic Biol Med. 2016 Feb;91:68-80
20. Inhibition of the Integrin/FAK Signaling Axis and c-Myc Synergistically Disrupts Ovarian Cancer Malignancy" by Yang X, Xu B, Lefringhouse J, Ueland F, Baldwin L, West D, Napier D, Chen Li, Chaiswing L, St Clair DK, Occoner K, Brewer L, Thibault O, Zhou B, Liu Z, Huang JA, Drapkin R, and Lu M. Oncogene 2016 (in press).
21. Wei1 X, Xu Y, Xu FF, Chaiswing L, Schnell DM, Noel Tl, Wang C, Chen J, St. Clair DK, and St. Clair WH. RelB is a central regulator that adjudicates the differential effects of ascorbic acid in normal and cancer cell. Cancer Research 2016 (in press).
Peer-Reviewed Original Research in Professional, Scientific or Educational Journals
1. St Clair D, Zhao Y, Chaiswing L, Oberley TD. Modulation of skin tumorigenesis by SOD. Biomed Pharmacother. 2005, May;59(4):209-14.
2. Chaiswing L, Oberley TD. Extracellular/Microenvironmental Redox State. Antioxid Redox Signal. 2010, Aug 15;13(4):449-65.
Books, Book Chapters, Monographs
1. Author of the book chapter entitled “Superoxide, superoxide dismutase and cardiovascular disease” in Advances in Cell Aging and Gerontology. 2002, Vol. 11, 233-281. ISBN: 0-444-51159-8.
2. Author of the book chapter entitled “Redox State and Prostate Cancer Behavior” in Handbook of Prostate Cancer Cell Research: Growth, Signaling and Survival. 2009, 4th Quarter, 489-94. Editor: Alan T. Meridith. ISBN: 978-1-60741-954-9.
Web blog: "Beyond the Abstract" at Urotoday.com.