Abstract 1083: Alpha-santalol, a chemopreventive agent against skin cancer, causes G2/M cell cycle arrest in both p53 mutated human epidermoid carcinoma A431 cells, and p53 wild-type human melanoma UACC-62 cells

Abstract

Abstract α-Santalol, an active component of sandalwood oil, has shown chemopreventive effects on skin cancer development in murine models by either chemical- or UVB-induced skin carcinogenesis. α-Santalol has shown induction of apoptosis in both murine models and epidermoid carcinoma A431 cells. However, to the best of our knowledge, effects of α-santalol on cell cycle have not been studied. Thus, the objective of this study was to investigate the effects of α-santalol on cell cycle progression and protein components involved in the regulation of cell cycle in both p53 mutated human epidermoid carcinoma A431 cells and p53 wide-type human melanoma UACC-62 cells to elucidate the mechanism(s) of action. MTT assay was used to determine cell viability in A431 cells, UACC-62 cells and monkey kidney CV-1 cells; fluorescence-activated cell sorting (FACS) analysis of propidium iodide staining was used for determining cell cycle distribution in A431 cells and UACC-62 cells, and Western immunoblotting was used for determining the expression of various proteins involved in the cell cycle progression. Results showed that α-santalol at concentration of 25 to 75 μM resulted in a concentration-and time-dependent decrease in cell viability from 24 h treatment in both A431 and UACC-62 cells. Cell cycle analysis by flow cytometry showed that α-santalol at 50 μM and 75 μM induced G2/M phase cell cycle arrest starting from 6 hour treatment in both UACC-62 and A431 cells. Furthermore, Western immunoblotting data showed that α-santalol altered the expressions of cell cycle proteins such as cyclin A, cyclin B1, cell division cycle 2 (cdc2), cdc25c and cyclin-dependent kinase 2 (Cdk2) in A431 cells which are required for G2/M transition. α-Santalol treatment upregulated the expression of p21CIP1/WAF1 and suppressed the expression of mutated p53 in A431 cells; whereas, α-santalol treatment increased the expressions of wide-type p53 in UACC-62 cells. Taken together, this study for the first time identifies the effects of α-santalol in G2/M phase arrest and describes the detailed mechanisms of G2/M phase arrest by this agent in both p53 mutated A431 cells and p53 wide-type UACC-62 cells, which might be contributing to its overall cancer preventive efficacy in various mouse skin cancer models in addition to induction of apoptosis by α-santalol. (Supported by 2010 Research Initiative Grant from the State of South Dakota funded as Translational Cancer Research Center). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1083.