Abstract 2254: A novel chemopreventive mechanism for a traditional medicine: East Indian sandalwood oil induces autophagy and cell death in proliferating keratinocytes

α-Santalol, one of the primary components of the East Indian sandalwood oil (EISO), has been investigated for its potential use as a chemopreventive agent in skin cancer. Although there is some evidence that α-santalol could be an effective chemopreventive agent, to date, purified EISO has not been investigated. EISO is widely used for its health benefits in cultures around the world. In the current study, we show for the first time that EISO-treatment of cultured keratinocytes inhibits cell cycle progression and UV-induced AP-1 activity, two major cellular effects known to drive skin carcinogenesis. Unlike many chemopreventive agents, inhibition of signaling upstream of AP-1 was not a primary means of EISO-mediated AP-1 inhibition, as no effect of EISO was observed on UV-induced Akt, ERK, and p38 MAPK activity. EISO induced cell death at low concentrations, although caspase and PARP cleavage were not observed indicating that death was not due to apoptosis. Interestingly, plasma membrane integrity was severely compromised in EISO-treated cells and LC3 cleavage suggests the induction of autophagy. These effects were more pronounced in EISO-treated cells that were stimulated to proliferate than in quiescent cells. Together, these effects suggest that EISO has chemopreventive properties and may be useful as in preventing skin carcinogenesis. Citation Format: Corey Levenson, Erik R. Olson, David S. Alberts, G. Tim Bowden. A novel chemopreventive mechanism for a traditional medicine: East Indian sandalwood oil induces autophagy and cell death in proliferating keratinocytes. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2254. doi:10.1158/1538-7445.AM2013-2254