Antitumour Activity of Simvastatin
Statins (for ex. Atrovastatin, Simvastatin, etc.), inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, are efficient and widely used drugs in the treatment of lipid disorders, especially hypercholesterolemia. In addition to their cholesterol-lowering effects, statins are reported to inhibit tumour cell growth, enhance the effects of chemotherapy and overcome chemoresistance .
It is reported that cancer cells overexpress HMG-CoA reductase . Statins help in inhibition of HMG-CoA reductase in cholesterol synthesis and thereby, also inhibits cell growth . Although it is postulated that statins lead to apoptotic cell death through their inhibition of the mevalonate pathway, few other mechanisms also have been suggested . Statins are reported to inhibit the activation of protein ras , influence production of Interleukin-18 (IL-18) , and control angiogenesis.
Researchers investigating the potential effects of Simvastatin on Renal cell carcinoma (RCC) cells and mechanisms by which Simvastatin exerted its actions, published the following results :
1. Simvastatin potently suppressed cell growth of A498 and 786-O cells in a time- and dose- dependent manner.
2. The xenograft model performed in nude mice exhibited reduced tumor growth with simvastatin treatment.
3. The inhibitory effects of Simvastatin on migration and invasion were also observed in vitro.
4. Simvastatin could suppress the proliferation and motility of RCC cells via inhibiting the phosphorylation of AKT, mTOR, and ERK in a time- and dose- dependent manner.
5. Simvastatin could exert the anti-tumor effects by suppressing IL-6-induced phosphorylation of JAK2 and STAT3.
These results suggest that Simvastatin may be a potential therapeutic agent for the treatment of RCC patients.
1. Nishibori, M.; et. al. The antitumour activities of statins. Curr Oncol 2007, 14(6), 246.
2. Hentosh, P.; et. al. Sterol-independent regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase in tumor cells. Mol Carcinog 2001, 32, 154-66.
3. Buchwald, H. Cholesterol inhibition, cancer, and chemotherapy. Lancet 1992, 339, 1154-1156.
4. Wong , W. W.; et. al. hmg-coa reductase inhibitors and the malignant cell: the statin family of drugs as triggers of tumor-specific apoptosis. Leukemia 2002, 16, 508-19.
5. Takahashi H. K.; et. al. Simvastatin induces interleukin-18 production in human peripheral blood mononuclear cells. Clin Immunol 2005, 116, 211-126.
6. Liu, Z.; et. al. Simvastatin Inhibits Renal Cancer Cell Growth and Metastasis via AKT/mTOR, ERK and JAK2/STAT3 Pathway. PLoS One. 2013, 8(5), e62823.