Elimination of ALDH+ breast tumor initiating cells by docosahexanoic acid and/or gamma tocotrienol through SHP-1 inhibition of Stat3 signaling.

Abstract

Study investigated the ability of docosahexaenoic acid (DHA) alone and in combination with gamma-tocotrienol (γT3) to eliminate aldehyde dehydrogenase positive (ALDH+) cells and to inhibit mammosphere formation, biomarker and functional assay for tumor initiating cells (TICs), respectively, in human triple negative breast cancer cells (TNBCs), and investigated possible mechanisms of action. DHA upregulated Src homology region 2 domain-containing protein tyrosine phosphatase-1 (SHP-1) protein levels and suppressed levels of phosphorylated signal transducer and activator of transcription-3 (pStat3) and its downstream mediators c-Myc, and cyclin D1. siRNA to SHP-1 enhanced the percentage of ALDH+ cells and Stat-3 signaling, as well as inhibited, in part, the ability of DHA to reduce the percentage of ALDH+ cells and Stat-3 signaling. γT3 alone and in combination with DHA reduced ALDH+ TNBCs, up-regulated SHP-1 protein levels, and suppressed Stat-3 signaling. Taken together, data demonstrate the anti-TIC potential of achievable concentrations of DHA alone as well as in combination with γT3.

• Authors: Ailian Xiong, Weiping Yu, Yaobin Liu, Bob G Sanders, Kimberly Kline
• Journal: Molecular carcinogenesis (Mol Carcinog) Vol. 55 Issue 5 Pg. 420-30 (May 2016) ISSN: 1098-2744 [Electronic] United States
• PMID: 25648304 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 Wiley Periodicals, Inc.

Chemical References

• Chromans
• STAT3 Transcription Factor
• STAT3 protein, human
• Vitamin E
• Docosahexaenoic Acids
• plastochromanol 8
• Aldehyde Dehydrogenase
• PTPN6 protein, human
• Protein Tyrosine Phosphatase, Non-Receptor Type 6

Topics

• Aldehyde Dehydrogenase (metabolism)
• Antineoplastic Combined Chemotherapy Protocols
• Cell Line, Tumor
• Chromans (pharmacology)
• Docosahexaenoic Acids (pharmacology)
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Neoplastic Stem Cells (drug effects, enzymology)
• Phosphorylation (drug effects)
• Protein Tyrosine Phosphatase, Non-Receptor Type 6 (metabolism)
• STAT3 Transcription Factor (metabolism)
• Signal Transduction (drug effects)
• Triple Negative Breast Neoplasms (enzymology, metabolism)
• Vitamin E (analogs & derivatives, pharmacology)