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 [1].
It is reported that cancer cells
overexpress HMG-CoA reductase [2]. Statins help in inhibition of HMG-CoA
reductase in cholesterol synthesis and thereby, also inhibits cell growth [3].
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 [4]. Statins are reported to
inhibit the activation of protein ras [4], influence production of Interleukin-18
(IL-18) [5], 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 [6]:
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.
References:
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.
