Journal
MOLECULAR CARCINOGENESIS
Volume 55, Issue 5, Pages 420-430Publisher
WILEY
DOI: 10.1002/mc.22291
Keywords
aldehyde dehydrogenase activity positive (ALDH plus ); cancer stem-like cells (CSCs); docosahexaenoic acid (DHA); gamma-tocotrienol (T3); mammospheres; protein Src homology region 2 domain-containing tyrosine phosphatase (SHP-1); signal transducer and activator of transcription 3 (Stat-3); triple negative breast cancer (TNBC) cells; tumor initiating cells (TICs)
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Funding
- Clayton Foundation for Research
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Study investigated the ability of docosahexaenoic acid (DHA) alone and in combination with gamma-tocotrienol (T3) 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. T3 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 T3. (c) 2015 Wiley Periodicals, Inc.
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