Eliminating drug resistant breast cancer stem-like cells with combination of simvastatin and gamma-tocotrienol.

Abstract

Present study shows that drug resistant human breast cancer cells are enriched in cancer stem-like cells (CSCs) and express elevated levels of Stat-3 signaling mediators, which contribute to CSC enrichment. Simvastatin (SVA) and gamma-tocotrienol (γT3) eliminate enriched CSCs and suppress expression of Stat-3 signaling mediators via inhibition of the mevalonate pathway and activation of de novo ceramide synthesis pathway, respectively. Combination of SVA+γT3 at low doses enhanced these actions via inhibition of the mevalonate pathway. Data demonstrate that SVA and γT3 alone or in combination possess the ability to eliminate CSCs in drug resistant human breast cancer cells.

• Authors: Archana Gopalan, Weiping Yu, Bob G Sanders, Kimberly Kline
• Journal: Cancer letters (Cancer Lett) Vol. 328 Issue 2 Pg. 285-96 (Jan 28 2013) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 23063651 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Antigens, CD
• Ceramides
• Chromans
• STAT3 Transcription Factor
• Vitamin E
• plastochromanol 8
• Simvastatin
• Retinal Dehydrogenase
• Mevalonic Acid

Topics

• Antigens, CD (metabolism)
• Antineoplastic Combined Chemotherapy Protocols (pharmacology)
• Breast Neoplasms (genetics, metabolism)
• Cell Line, Tumor
• Ceramides (biosynthesis)
• Chromans (pharmacology)
• Drug Resistance, Neoplasm
• Drug Synergism
• Female
• Humans
• Mevalonic Acid (metabolism)
• Neoplastic Stem Cells (drug effects, metabolism)
• Retinal Dehydrogenase (metabolism)
• STAT3 Transcription Factor (metabolism)
• Signal Transduction (drug effects)
• Simvastatin (pharmacology)
• Vitamin E (analogs & derivatives, pharmacology)