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Elimination of ALDH+ breast tumor initiating cells by docosahexanoic acid and/or gamma tocotrienol through SHP‐1 inhibition of Stat3 signaling
Author(s) -
Xiong Ailian,
Yu Weiping,
Liu Yaobin,
Sanders Bob G.,
Kline Kimberly
Publication year - 2016
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.22291
Subject(s) - biology , aldehyde dehydrogenase , cancer research , stat3 , cyclin d1 , stat protein , signal transduction , microbiology and biotechnology , protein tyrosine phosphatase , biochemistry , apoptosis , cell cycle , enzyme
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. © 2015 Wiley Periodicals, Inc.