The non-pungent N-AVAM capsaicin analog DOHEVANIL displays robust growth-suppressive activity in human endrometriod ovarian cancers in vitro and in vivo

Purpose of the Study : Endometrioid ovarian carcinomas (EOC) account for ~10% (range 8-15%) of all ovarian cancers. They are considered the second most common malignant ovarian neoplasm, after high-grade serous ovarian cancer (HGSOC). EOCs tumors are characterized by complex tubular and solid-cystic masses. The development of EOC may occur as a secondary event to an endometriosis lesion. The first line-treatment for EOC is surgery and combination chemotherapy involving platinum drugs and taxanes. However, most EOC patients become resistant to chemotherapy and the disease relapses within 12-36 months. Several lines of evidence show that nutritional compounds display robust anti-cancer activity in human cancers. Our laboratory observed that capsaicin (the spicy component of chili peppers) potently inhibited the growth of human EOCs. However, the clinical application of capsaicin as a viable anti-cancer drug is limited by its adverse side effect profile. Using SAR studies, we have identified a non-pungent analog of capsaicin, namely Dohevanil. The primary objective of this research project was to explore the growth-hindering activity of gemcitabine and Dohevanil in EOCs. Experimental Procedures : MTT assays used to measure perform SAR studies in human EOC cell lines. The growth-suppressive activity of Dohevanil was tested in both human EOC cell lines and in normal human epithelial cells. The results obtained from the MTT assays were confirmed using the chicken chorioallantoic membrane (CAM) assay. Finally, the anti-cancer activity of Dohevanil was evaluated in SCID mouse tumor xenograft models of EOCs. Results : Dohevanil displayed robust growth inhibitory activity in human EOC cell lines and in chicken CAM and mouse models Conclusions : Non-pungent capsaicin analogs like Dohevanil may be useful adjunct therapies in human EOCs. 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.