Simvastatin inhibition of mevalonate pathway induces apoptosis in human breast cancer cells via activation of JNK/CHOP/DR5 signaling pathway

• Published in: Cancer letters Vol. 329; no. 1; pp. 9 - 16
• Main Authors: Gopalan, Archana, Yu, Weiping, Sanders, Bob G, Kline, Kimberly
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 01.02.2013; Elsevier Limited
• Subjects: Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; binding proteins; Biomarkers; Breast cancer; breast neoplasms; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; c-Jun N-terminal kinase (JNK); CCAAT/enhancer binding protein homologous protein (CHOP); Cell culture; Cell Line, Tumor; coenzyme A; death; Death receptor-5 (DR5); Female; Free radicals; Hematology, Oncology and Palliative Medicine; Human breast cancer cells; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology; JNK Mitogen-Activated Protein Kinases - genetics; JNK Mitogen-Activated Protein Kinases - metabolism; MAP Kinase Signaling System - drug effects; Mevalonic Acid - metabolism; mitogen-activated protein kinase; Polyisoprenyl Phosphates - pharmacology; Receptors, TNF-Related Apoptosis-Inducing Ligand - genetics; Receptors, TNF-Related Apoptosis-Inducing Ligand - metabolism; RNA, Small Interfering; Sesquiterpenes - pharmacology; signal transduction; Signal Transduction - drug effects; Simvastatin (SVA); Simvastatin - pharmacology; Studies; Transcription Factor CHOP - genetics; Transcription Factor CHOP - metabolism; c-Jun N-terminal kinase (JNK); Simvastatin (SVA); CCAAT/enhancer binding protein homologous protein (CHOP); Death receptor-5 (DR5); Human breast cancer cells; Apoptosis
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2012.08.031

Highlights ► Lipophilic statin, simvastatin, triggers apoptosis in human breast cancer cells via JNK/CHOP/DR5 dependent signaling. ► Simvastatin blockage of mevalonate and geranylgeranyl pyrophosphate is critical for pro-death effect. ► Death Receptor 5 protein levels are upregulated by simvastatin and necessary for simvastatin-induced apoptosis.