Abstract 1782: Post-translational regulation of cyclins by Aspirin through 26S proteasome: Implications in chemoprevention

Abstract Recent studies have shown that, regular use aspirin for 5 years or more, decreases the occurrence of cancer of the colon, skin, breast, prostate and lung tissues. However, the mechanism of its anti-cancer effects are not completely understood. We hypothesized that Aspirin's chemo preventive action may involve proteins important in the regulation of cell cycle. Using multiple colon and skin cancer cells, we studied whether aspirin modulates the expression of cyclin B1. Cyclin B1 is a regulatory protein involved in mitosis and promotes the passage of cell cycle from G2 to M phase. Cyclin B1 along with Cyclin dependent Kinase 1(CDK1) regulates chromosomal condensation, nuclear envelope break down and spindle pole assembly in early mitosis. We demonstrate that, in HT-29 human colon and Sk-Mel 28 skin cancer cells, aspirin dose dependently decreased the levels of cyclin B1. This was further confirmed using immunofluorescence studies. To determine the involvement of proteases, we determined whether the lactacystin, a 26S proteasomal inhibitor, would reverse the inhibitory effect of aspirin on cyclin B1. We observed that pretreatment of cells with lactacystin completely reversed the decrease in levels of cyclin B1 in aspirin treated cells. Transfection of the DDK tagged cyclin B1 into HT-29 cells were carried out to establish whether the decrease observed occurs through a nuclear independent and post-translational mechanism. We observed that, aspirin significantly decreased the exogenously transfected DDK tagged cyclin B1 protein. Our results, for the first time show that anticancer effects of aspirin may occur through cyclin B1 degradation mediated by 26S proteasomes. Citation Format: Rakesh Dachineni, Guoqiang Ai, Hemachand Tummala, Jayarama B. Gunaje. Post-translational regulation of cyclins by Aspirin through 26S proteasome: Implications in chemoprevention. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1782. doi:10.1158/1538-7445.AM2015-1782