Home
Resources
Publications
Involvement of Oxidative Stress in Simvastatin-Induced Apoptosis of Murine CT26 Colon Carcinoma Cells

Involvement of Oxidative Stress in Simvastatin-Induced Apoptosis of Murine CT26 Colon Carcinoma Cells

Xu-Feng Qi, Dong-Heui Kim, Yang-Suk Yoon, Soo-Ki Kim, Dong-Qing Cai, Yung-Chien Teng, Kwang-Yong Shim, Kyu-Jae Lee

Toxicol Lett. 2010 Dec 15;199(3):277-87.

PMID: 20883752

Abstract:

Recent studies have suggested that oxidative stress may play a role in the cytotoxic activity of statins against cancer cells. The objective of this study was to elucidate the role of oxidative stress in the cytotoxicity of simvastatin in murine CT26 colon carcinoma cells and B16BL6 melanoma cells. We found that CT26 cells were more sensitive to simvastatin than B16BL16 cells. Interestingly, exposure to simvastatin causes significant apoptotic cell death and perturbations in parameters indicative of oxidative stress in CT26 cells. Moreover, the increase in oxidative stress parameters and cell death were suppressed by isoprenoids including mevalonolactone, farnesyl pyrophosphate ammonium salt, geranylgeranyl pyrophosphate ammonium salt, and coenzyme Q10, and by antioxidants including N-acetyl cysteine, reduced glutathione, superoxide dismutases (SOD), and catalase (CAT) alone or in combination, but were promoted by an inhibitor of glutathione synthesis, L-buthionine-sulfoximine. The signaling pathway induced by simvastatin breaks down the antioxidant defense system by suppressing the expression of reactive oxygen species scavengers, particularly Mn-SOD, CAT, GPx1, and SESN 3, thereby inducing oxidative stress and apoptotic cell death. Collectively, our results demonstrate that simvastatin induces colon cancer cell death at least in part by increasing intracellular oxidative stress and inducing apoptosis.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
ALP6699203	Geranylgeranyl pyrophosphate ammonium salt		6699-20-3 (free acid)	Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: