RESVERATROL MODULATES CISPLATIN OXIDATIVE STRESS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The West Virginia IDeA Network of Biomedical Research Excellence (WV-INBRE) has successfully established a research experience for undergraduate students and established a research network between the lead institition and partner institutions. This supplemental translational research proposal will further grow and establish the primary goals of the WV-INBRRE parent award. The supplement will further increase translational biomedical research opportunities/activities for undergraduate students and faculty at a partner institution (West Virginia Wesleyan College). The supplement will also foster interactions between WV-INBRE and another NCRR Program (COBRE). Additional individuals will be hired which will increase the workforce and tempo of scientific research conducted by American undergraduates, faculty and technical staff in WV. The scientific focus will be on cancer, which is one of the mutlidisciplinary research themes of the parent WV-INBRE award. Cancer is a major health concern and is the second leading cause of death in the U.S. Breast cancer afflicts 1 in 8 women in the U.S., and one of the cancer chemotherapeutic agents used to treat breast cancer is cisplatin. Unfortunately, cisplatin induces irreversible renal damage is some patients. Dr. Valentovic, a faculty member of the Marshall University School of Medicine, has established an in vitro model in which resveratrol (RES) reduces cisplatin renal toxicity. The research goal of this supplement is to establish the mechanism for RES attenuation of cisplatin renal toxicity. This project will focus on whether RES enhances renal excretion of cisplatin or reduces renal accumulation as part of its protective mechanism. This proposal will further examine whether reduction of oxidative stress is part of the cellular mechanism of RES protection for cisplatin toxicity. RES has been shown to inhibit tumor growth for some cancer cells, and the final aim of this translational project will be the first study to examine whether the combination of RES and cisplatin is more effective than cisplatin alone to slow breast cancer cell growth. Administration of an agent such as RES to reduce cisplatin toxicity and possibly improve tumor kill would be of immediate human health benefit to cancer chemotherapy patients.