title: Α-eleostearic acid inhibits growth and induces apoptosis in breast cancer cells via HER2/HER3 signaling.
abstract: α-eleostearic acid (α-ESA) has been shown to possess antitumor activity in cancer cells. However, the underlying mechanism(s) remain largely unknown. The present study was designed to investigate the antitumor effect of α-ESA in breast cancer cells showing different expression levels of the human epidermal growth factor receptor 2 (HER2). α-ESA inhibited cell growth and induced apoptosis in the SKBR3 and T47D breast cancer cell lines. The mechanism by which cell growth was inhibited involved G0/G1 and G2/M cell cycle phase arrest. The MTT assay showed that SKBR3 cells are more sensitive to α-ESA compared to T47D cells. Western blot analysis revealed that α-ESA treatment not only reduced HER2/HER3 protein expression, but also increased the level of phosphorylated phosphatase and tensin homolog protein (PTEN), which led to decreased levels of phosphorylated Akt. Inactive Akt further reduced phosphorylation of glycogen synthase kinase-3β (GSK-3β) and B-cell lymphoma 2 (Bcl-2)‑associated death promoter (BAD) proteins. Furthermore, the level of the anti-apoptotic protein Bcl-2 was found to be reduced following α-ESA treatment. Notably, nuclear factor κB (NF-κB) was activated by α-ESA treatment. Data of the present study showed that the antitumor activity of α-ESA is at least partly mediated by reduction of the HER2/HER3 heterodimer protein level, activation of the Akt/BAD/Bcl-2 apoptotic pathway and inhibition of the Akt/GSK-3β survival pathway in the two breast cancer cell lines investigated in this study. Therefore, α-ESA may be considered a beneficial dietary factor for the prevention and treatment of invasive breast cancer in cells overexpressing HER2.
authors.affiliation: Medical School, Ningbo University, Ningbo, Zhejiang 315211, P.R. China.
authors.forename: Ren-Jie
authors.initials: RJ
authors.lastname: Zhuo
authors.affiliation: Clinical Laboratory, Lihuili Hospital, Ningbo, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Medical School, Ningbo University, Ningbo, Zhejiang 315211, P.R. China.
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Zhang
authors.affiliation: Maritime Faculty, Ningbo University, Ningbo, Zhejiang 315211, P.R. China.
authors.forename: Jin-Jie
authors.initials: JJ
authors.lastname: Zhang
authors.affiliation: Medical School, Ningbo University, Ningbo, Zhejiang 315211, P.R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Xu
authors.affiliation: Medical School, Ningbo University, Ningbo, Zhejiang 315211, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Dong
authors.affiliation: Medical School, Ningbo University, Ningbo, Zhejiang 315211, P.R. China.
authors.forename: Zu-Quan
authors.initials: ZQ
authors.lastname: Zou
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000378:metabolism / Q000503:physiopathology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D008042:Linolenic Acids / Q000494:pharmacology*; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D020893:Receptor, ErbB-3 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D051025:bcl-Associated Death Protein / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D038362:Glycogen Synthase Kinase 3; D000071679:Glycogen Synthase Kinase 3 beta; D008042:Linolenic Acids; D051059:PTEN Phosphohydrolase; D051057:Proto-Oncogene Proteins c-akt; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D051025:bcl-Associated Death Protein; C004934:eleostearic acid; C508053:ERBB2 protein, human; C581292:ERBB3 protein, human; C000605506:GSK3B protein, human; C494929:PTEN protein, human