Abstract 6834: The Region C non-pungent capsaicin analogs ARVANIL and DOHEVANIL sensitize human ovarian cancer cells towards the growth-inhibitory activity of gemcitabine

Abstract Purpose of the Study: Ovarian cancer (OC) is the second most common gynecologic cancer in the United States. Ovarian cancer causes more deaths than any other cancer (of the female reproductive system) in women. Combination chemotherapy involving cisplatin and taxanes is the cornerstone for ovarian cancer treatment. The challenge with ovarian chemotherapy is that patients develop cisplatin-resistance (and/or taxane-resistance) upon prolonged exposure to the drug. Gemcitabine is one of the second-line therapies for relapsed ovarian cancer. Several convergent studies show that nutritional phytochemicals can often improve the therapeutic response of chemotherapeutic drugs. The long-term objective of our laboratory is to identify dietary chemicals that may improve the anti-cancer activity of chemotherapeutic drugs. Our published data show that capsaicin (the spicy component of chili peppers) enhanced the pro-apoptotic activity of the chemotherapy drug camptothecin in human small-cell lung cancers. Apart from capsaicin, we have also identified non-pungent capsaicin analogs namely ARVANIL and DOHEVANIL which display greater growth-inhibitory activity in human Ovarian carcinoma cells relative to capsaicin. The objective of the present research project was to explore the combinatorial activity of gemcitabine and these capsaicin analogs in ovarian cancer. Experimental Procedures: Caspase-3 Activity Assays and Cell Death ELISA assays were used to measure the pro-apoptotic activity of the combination of gemcitabine and Arvanil in human ovarian cancer cells. We also determined the combinatorial pro-apoptotic activity of gemcitabine and dohevanil in human ovarian cancer cells. The results obtained from the apoptosis assays were confirmed using the soft agar assay and the chicken chorioallantoic membrane assay. Results: Both arvanil and dohevanil sensitized human ovarian cancer cells towards the growth-inhibitory activity of capsaicin Conclusions: The combination of platinum drugs with capsaicin and capsaicin-like compounds may improve the pro-apoptotic activity of cisplatin in human ovarian cancer. Support or Funding Information Funding for our study was supported by the NIH R15-AREA Grant (2R15CA161491-02 and 2R15CA161491-03), the Women's Health T3: 3P20GM103434-23W1 (PI: Dr. G Rankin) to PD and MAV and the NIAID-AI151970 grant to TEL. Furthermore, this study was supported in part by the West Virginia IDeA Network of Biomedical Research Excellence (WV-INBRE) grant (NIH grant P20GM103434; PI: Dr. G. Rankin), the National Institute of General Medical Sciences of the National Institutes of Health under the award number P30GM122733. Citation Format: Kaitlyn B. Conley, Stephen D. Richbart, Kushal J. Modi, Reagan S. Light, Rama S. Gadepalli, John R. Rimoldi, Timothy E. Long, Yi Charlie Chen, Piyali Dasgupta. The Region C non-pungent capsaicin analogs ARVANIL and DOHEVANIL sensitize human ovarian cancer cells towards the growth-inhibitory activity of gemcitabine [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6834.