title: Dual Inhibition of Key Proliferation Signaling Pathways in Triple-Negative Breast Cancer Cells by a Novel Derivative of Taiwanin A.
abstract: The treatment of breast cancer cells obtained by blocking the aberrant activation of the proliferation signaling pathways PI3K/Akt/mTOR and MEK/ERK has received considerable attention in recent years. Previous studies showed that Taiwanin A inhibited the proliferation of several types of cancer cells. In this study, we report that 3,4-bis-3,4,5-trimethoxybenzylidene-dihydrofuran (BTMB), a novel derivative of Taiwanin A, significantly inhibited the proliferation of triple-negative breast cancer (TNBC) cells bothin vitroandin vivoThe results show that BTMB inhibited the proliferation of human TNBC cells by the induction of cell-cycle arrest and apoptosis in a dose-dependent fashion. BTMB inhibited the expression of β-catenin, cdc2 and the cell-cycle regulatory proteins, cyclin A, cyclin D1, and cyclin E. The mechanism of action was associated with the suppression of cell survival signaling through inactivation of the Akt and ERK1/2 signaling pathways. Moreover, BTMB induced cell apoptosis through an increase in the expression of BAX, cleaved caspase-3, and cleaved PARP. Moreover, BTMB inhibited TNBC cell colony formation and sensitized TNBC cells to cisplatin, a chemotherapeutic drug. In a TNBC mouse xenograft model, BTMB significantly inhibited the growth of mammary carcinomas through decreased expression of cyclin D1. BTMB was shown to significantly suppress the growth of mammary carcinoma and therefore to have potential as an anticancer therapeutic agent.Mol Cancer Ther; 16(3); 480-93. ©2016 AACR.
authors.affiliation: Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung, Taiwan, PR China.|Department of Biotechnology, Asia University, Taichung, Taiwan, PR China.
authors.forename: Yueh-Hsiung
authors.initials: YH
authors.lastname: Kuo
authors.affiliation: Department of Food Science and Biotechnology, National Chung Hsing University, Taichung, Taiwan, PR China.|NCHU-UCD Plant and Food Biotechnology Center, National Chung Hsing University, Taichung, Taiwan, PR China.|Agricultural Biotechnology Center, National Chung Hsing University, Taichung, Taiwan, PR China.
authors.forename: En-Pei Isabel
authors.initials: EI
authors.lastname: Chiang
authors.affiliation: Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan, PR China.|Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan, PR China.
authors.forename: Che-Yi
authors.initials: CY
authors.lastname: Chao
authors.affiliation: Department of Molecular and Cellular Biology, University of California, Davis, California.
authors.forename: Raymond L
authors.initials: RL
authors.lastname: Rodriguez
authors.affiliation: Biomedical Science Laboratory, Department of Nutrition, China Medical University, Taichung, Taiwan, PR China.
authors.forename: Pei-Yu
authors.initials: PY
authors.lastname: Chou
authors.affiliation: Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan, PR China.
authors.forename: Shu-Yao
authors.initials: SY
authors.lastname: Tsai
authors.affiliation: Department of Anatomy, Taipei Medical University, Taipei, Taiwan, PR China.
authors.forename: Man-Hui
authors.initials: MH
authors.lastname: Pai
authors.affiliation: Biomedical Science Laboratory, Department of Nutrition, China Medical University, Taichung, Taiwan, PR China. vincenttang@mail.cmu.edu.tw.
authors.forename: Feng-Yao
authors.initials: FY
authors.lastname: Tang
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D005663:Furans / Q000737:chemistry / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D017705:Lignans / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; D015415:Biomarkers; D018797:Cell Cycle Proteins; D005663:Furans; D017705:Lignans; C419332:taiwanin A; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases