title: Triticuside A, a dietary flavonoid, inhibits proliferation of human breast cancer cells via inducing apoptosis.
abstract: In this study we demonstrated that Triticuside A, one of the flavonoid compounds isolated from wheat bran, induced apoptosis and inhibited proliferation of human breast cancer cells. Triticuside A inhibited the proliferation of human breast cancer cells (MCF-7 and MDA-MB-231) in a dose-dependent manner but barely showed cytotoxicity to the normal human fibroblasts. Triticuside A-induced apoptosis was accompanied by a significant decrease of Mcl-1 and Bcl-2 proteins and by an increase of cleavage of caspases-3, -7, -9, and PARP. Triticuside A also suppressed the level of phospho-Akt and its downstream targets, mTOR and P70 S6 kinase. LY294002, a specific inhibitor of PI3K, significantly enhanced the Triticuside A-induced apoptosis. Moreover LY294002 not only downregulated the level of phospho-Akt but also enhanced the inhibition of Mcl-1 expression when combined with Triticuside A. Our results demonstrate for the first time the specific apoptogenic activity of Triticuside A in tumor cells and involvement of the mitochondrial apoptosis pathway and Akt/mTOR signaling pathway. Thus, Triticuside A may be a potentially useful wheat bran component that can be used for prevention or treatment of breast cancer.
authors.affiliation: Departments of Pharmacology, The Penn State Hershey Cancer Institute, The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033-0850, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Shan
authors.forename: Yan
authors.initials: Y
authors.lastname: Cheng
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Fu-Qin
authors.initials: FQ
authors.lastname: Guan
authors.forename: Hao
authors.initials: H
authors.lastname: Sun
authors.forename: Xing-cong
authors.initials: XC
authors.lastname: Ren
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.forename: Xu
authors.initials: X
authors.lastname: Feng
authors.forename: Jin-Ming
authors.initials: JM
authors.lastname: Yang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053179:Caspase 7 / Q000235:genetics / Q000378:metabolism; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002867:Chromones / Q000494:pharmacology; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D006027:Glycosides / Q000494:pharmacology*; D006801:Humans; D061986:MCF-7 Cells; D009025:Morpholines / Q000494:pharmacology; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000235:genetics / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D053148:Caspase 3; D053179:Caspase 7; D053453:Caspase 9; D002867:Chromones; D004791:Enzyme Inhibitors; D005419:Flavonoids; D006027:Glycosides; D009025:Morpholines; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; C579095:MCL1 protein, human; C090468:TP53BP2 protein, human; C586693:triticuside A; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C546842:MTOR protein, human; C505407:CASP3 protein, human; C505520:CASP7 protein, human; C506433:CASP9 protein, human