The synthetic non pungent capsaicin analog Arvanil displays robust anti-tumor activity in human small cell lung cancer.

The nutritional compound capsaicin is the hot spicy pungent ingredient of chili peppers. Capsaicin is a pain-relieving agent and is found in several over-the counter pain medications. However, recent studies have shown that capsaicin has profound anti-neoplastic effects in several types of human cancers. The applications of capsaicin as a clinically useful drug are limited by its unpleasant side effects, such as gastric irritation, stomach cramps and burning sensation. This has led to extensive research focused on the identification and rational design of second-generation capsaicin analogs, which possess greater bioactivity than capsaicin. Our laboratory performed an SAR study using a panel of non-pungent capsaicin analogs and identified Arvanil as the hit compound. Arvanil triggered robust apoptosis in a panel of human small cell lung cancer (SCLC). The growth-suppressive activity of Arvanil was confirmed in chicken chorioallantoic membrane (CAM) models. Finally, the dietary administration of Arvanil potently decreased the growth rate of human SCLC tumors xenotransplanted in athymic mice. The pro-apoptotic activity of Arvanil was mediated by the TRPV1 receptor and the calpain pathway. Non-pungent capsaicin analogs like Arvanil may be promising drug candidates for the management and treatment of human SCLC.