Eliminating drug resistant breast cancer stem-like cells with combination of simvastatin and gamma-tocotrienol.
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.
Department of Nutritional Sciences/A2703, University of Texas at Austin, Austin, TX 78712, USA.
Archana
A
Gopalan
Weiping
W
Yu
Bob G
BG
Sanders
Kimberly
K
Kline
D015703:Antigens, CD / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002518:Ceramides / Q000096:biosynthesis; D002839:Chromans / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D005260:Female; D006801:Humans; D008798:Mevalonic Acid / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism*; D050697:Retinal Dehydrogenase / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D019821:Simvastatin / Q000494:pharmacology*; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology
D015703:Antigens, CD; D002518:Ceramides; D002839:Chromans; D050796:STAT3 Transcription Factor; D014810:Vitamin E; C013649:plastochromanol 8; D019821:Simvastatin; D050697:Retinal Dehydrogenase; D008798:Mevalonic Acid