Non pungent capsaicin analogs and ovarian cancer therapy

Marshall University, Huntington WV

Investigators

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Abstract

PROJECT SUMMARY Capsaicin is the spicy, pungent ingredient of chili peppers. Traditionally, capsaicin is used as a pain-relieving agent in over-the counter creams and lotions. Published reports demonstrate that capsaicin displays robust growth-suppressive activity in human ovarian cancers. Apart from its direct growth-inhibitory activity, capsaicin sensitizes human ovarian cancer cells to the pro- apoptotic activity of the chemotherapy drug cisplatin. However, the development of capsaicin as a viable anti-cancer drug is limited by its unfavorable side effect profile. The administration of capsaicin causes nausea, stomach cramps and gut pain in patients. Such unpleasant side effects have led patients to abandon using the drug. Structure-Activity Relationship (SAR) studies have revealed that the addition of unsaturated long chain fatty acyl groups to the C-terminus of capsaicin yields non-pungent capsaicin analogs (called N-Acylvanillylamides or N-AVAMs) with robust analgesic activity. The present grant application aims to re-purpose these N-AVAMs and investigate their anti-cancer in human ovarian cancers. To achieve our objectives, we aim to screen the anti-cancer activity of a panel of six N-AVAMs in chicken chorioallantoic membrane (CAM) model of ovarian cancers. We will also examine the ability of N-AVAMs to sensitize human ovarian cancer tumors towards the growth-inhibitory activity of cisplatin in chicken CAM models and patient-derived xenograft mice models of ovarian cancer. The central hypothesis of this application is that non-pungent N-AVAMs will display anti-tumor activity in ovarian cancer in vivo and will sensitize ovarian cancer cells towards the growth-suppressive activity of cisplatin. The data obtained from our grant application will foster the development of novel nutrition-based combination therapies for ovarian cancer patients.