Prevention Research 6: Prevention of Aerodigestive Cancers Abstract #2469 Capsaicin induces apoptosis in human pancreatic cancer cells by activating mitochondrial death pathway Ian Humphreys, Sivakumar Loganathan and Sanjay K. Srivastava University of Pittsburgh Cancer Institute, Pittsburgh, PA Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States. It is one of the most aggressive human malignancies with an extremely poor prognosis and is highly resistant to radiation and chemotherapy. Recently, considerable efforts have been made to evaluate the chemotherapeutic potential of dietary agents against human malignancies. Moreover, epidemiological and experimental studies have demonstrated that several dietary agents are effective against breast, prostate, lung and colon cancers. Capsaicin, an active ingredient of red chili pepper (0.1-1%), is one such dietary agent that has been shown to exhibit significant chemopreventive activity against experimentally induced mutagenesis and tumorigenesis. Accordingly, current studies revealed that capsaicin inhibits proliferation and induces apoptosis in various cancer cells, however, its therapeutic effects against pancreatic cancer has never been investigated. In the present study, we demonstrate that capsaicin is antiproliferative and induces apoptosis in AsPC-1 human pancreatic cancer cells. Treatment of AsPC-1 cells with capsaicin increased both the expression of pro-apoptotic protein bax and cytochrome c release into the cytosol, in a dose-dependent manner. In addition, we observed the generation of reactive oxygen species (measured by the oxidation of DCFDA by flow cytometery) and disruption of mitochondrial membrane potential (determined by flow cytometery using JC-1) in AsPC-1 cells following exposure to capsaicin for 24h. Our results also demonstrate that exposure of AsPC-1 cells to capsaicin causes activation of caspase-3 and its downstream target PARP, thus resulting in apoptosis. Interestingly, all of these effects were significantly attenuated upon pretreatment of cells with the antioxidant, N-acetyl cysteine (NAC). This strongly suggest that capsaicin induces apoptosis in AsPC-1 cells by altering redox homeostasis and targeting the mitochondrial death pathway. Taken together, our results demonstrate for the first time, the anticancer activity of capsaicin against human pancreatic cancer cells and its potential use as a novel chemotherapeutic agent. [Supported in part by RO1 grant CA 106953 (to S.K.S.) awarded by the National Cancer Institute]. Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.