Dual Inhibition of Key Proliferation Signaling Pathways in Triple-Negative Breast Cancer Cells by a Novel Derivative of Taiwanin A
| Autor: | Feng-Yao Tang, Pei Yu Chou, Yueh-Hsiung Kuo, Man Hui Pai, Shu-Yao Tsai, Raymond L. Rodriguez, Che Yi Chao, En-Pei Isabel Chiang |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cancer Research Cell Survival Cyclin A Apoptosis Cell Cycle Proteins Triple Negative Breast Neoplasms Biology Lignans Mice 03 medical and health sciences 0302 clinical medicine Cyclin D1 Cell Line Tumor Animals Humans Furans Protein kinase B PI3K/AKT/mTOR pathway Cell Proliferation Cyclin Cyclin-dependent kinase 1 TOR Serine-Threonine Kinases Cell Cycle Antineoplastic Agents Phytogenic Xenograft Model Antitumor Assays Tumor Burden Cell biology Gene Expression Regulation Neoplastic Disease Models Animal 030104 developmental biology Oncology 030220 oncology & carcinogenesis Cancer cell biology.protein Female Signal transduction Apoptosis Regulatory Proteins Proto-Oncogene Proteins c-akt Biomarkers Signal Transduction |
| Zdroj: | Molecular Cancer Therapeutics. 16:480-493 |
| ISSN: | 1538-8514 1535-7163 |
| DOI: | 10.1158/1535-7163.mct-16-0011 |
| Popis: | 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 both in vitro and in vivo. The 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. |
| Databáze: | OpenAIRE |
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