Simvastatin induces apoptosis in human breast cancer cells: p53 and estrogen receptor independent pathway requiring signalling through JNK
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CitationKoyuturk M, Ersoz M, Altiok N. Simvastatin induces apoptosis in human breast cancer cells: p53 and estrogen receptor independent pathway requiring signalling through JNK. Cancer Lett. 2007 Jun 8;250(2):220-8. doi:10.1016/j.canlet.2006.10.009
The effect of simvastatin, a widely used statin for the treatment of hypercholesterolemia, was investigated in the estrogen receptor (ER)-positive MCF-7, and the ER-negative MDA-MB 231 human breast cancer cell lines. Simvastatin induced cell cycle arrest and apoptosis in both cells. These effects of simvastatin were not altered by 17-β-estradiol treatment. MCF-7 cells express wild-type tumor suppressor protein p53, whereas MDA-MB 231 cells carry a p53 mutation. However, no alteration in the level or localisation of p53 was observed with simvastatin treatment in either cell line. On the other hand, simvastatin strongly stimulated phosphorylation of c-jun which was completely abolished by the c-jun NH2-terminal kinase (JNK) inhibitor SP600125, which also significantly reduced the antiproliferative and apoptotic effects of simvastatin in these cells.