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

Research output: Contribution to journalArticle

30 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)277-287
Number of pages11
JournalToxicology Letters
Volume199
Issue number3
DOIs
Publication statusPublished - 2010 Dec 15

Fingerprint

Oxidative stress
Simvastatin
Colon
Oxidative Stress
Cells
Cell death
Apoptosis
Carcinoma
Cell Death
coenzyme Q10
Ammonium Compounds
Catalase
Superoxide Dismutase
Glutathione
Salts
Antioxidants
Acetylcysteine
Buthionine Sulfoximine
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Terpenes

All Science Journal Classification (ASJC) codes

  • Toxicology

Cite this

Qi, Xu Feng ; Kim, Dong Heui ; Yoon, Yang Suk ; Kim, Soo Ki ; Cai, Dong Qing ; Teng, Yung Chien ; Shim, Kwang Yong ; Lee, Kyu Jae. / Involvement of oxidative stress in simvastatin-induced apoptosis of murine CT26 colon carcinoma cells. In: Toxicology Letters. 2010 ; Vol. 199, No. 3. pp. 277-287.
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Involvement of oxidative stress in simvastatin-induced apoptosis of murine CT26 colon carcinoma cells. / Qi, Xu Feng; Kim, Dong Heui; Yoon, Yang Suk; Kim, Soo Ki; Cai, Dong Qing; Teng, Yung Chien; Shim, Kwang Yong; Lee, Kyu Jae.

In: Toxicology Letters, Vol. 199, No. 3, 15.12.2010, p. 277-287.

Research output: Contribution to journalArticle

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