Abstract 1855: Statins decrease the expression of c myc in cancer cell lines

Abstract The widely used statin drugs for the prevention of cardiovascular diseases are envisioned to have the potential to control cancer. Repurposing these cardiovascular drugs for cancer prevention and/or treatment is an attractive proposition as these drugs are commonly prescribed in the clinic. However, there was no clinical evidence for statins being used as chemopreventive agents and the reasons for this are unclear. To further establish the effectiveness of statins as chemopreventive agents, we investigated the effects of three most common statins, simvastatin, atorvastatin and lovastatin on six different cancer cell lines including an ovarian cancer cell line that overexpresses P-glycoprotein, an ABCB1 gene product. Incubation of cells with statins (at both 12.5 microM and 25 microM) resulted in decreased cell growth in a time-dependent manner. The decreased cell growth could be correlated with decreased cellular NADPH levels. Measurement of viable and dead cells in statin treatments indicated that statins induced cell proliferation arrest without inducing cell death. Removal of statins from culture medium resulted in robust cell growth, identical to that observed in controls. Further, cell cycle analysis clearly indicated that statins induced cell cycle arrest at G0/G1 phase without inducing apoptosis. Analysis of the mechanism of statins in these cancer cells indicated that these drugs inhibit HMG CoA reductase, without affecting the transcript of the HMGCR. The HMG CoA reductase inhibition could be relieved with mevalonate. Analysis of key target proteins important for cancer cell proliferation identified that exposure of cancer cells to statins significantly decreased c-Myc protein without affecting its transcription. Importantly, removal of statins reversed the c-Myc expression to the normal level. Finally, incubation of cells with statins increased phosphorylation of H2AX, suggesting that statins promote cellular senescence. These data together suggested that statins are cytostatic, and eliminate c-Myc expression. These observations are consistently observed in the multidrug-resistant cells as well. These data lend strong support that statins could serve as excellent agents for cancer chemoprevention. Citation Format: U.S. Rao, Randy Mullins, Prema Rao. Statins decrease the expression of c myc in cancer cell lines [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1855.