Trastuzumab in combination with AT-101 induces cytotoxicity and apoptosis in Her2 positive breast cancer cells
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Date
2019
Authors
Bulut G.
Atmaca H.
Karaca B.
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Abstract
Aim: AT-101 is a polyphenolic compound with potent anti-apoptotic effects in various cancers. In this study, the possible synergistic cytotoxic and apoptotic effect of trastuzumab/AT-101 combination was investigated in HER2-positive breast cancer cell lines. Materials & methods: SKBR-3, MDA-MB-453 and MCF-10A cell lines were treated with a trastuzumab/AT-101 combination. Synergistic cytotoxicity and apoptosis effects were shown and then PI3K and Akt protein levels were studied. Result: The trastuzumab/AT-101 combination induced synergistic cytotoxicity and apoptosis in both breast cancer cells but not in MCF-10A cells. Combination treatment induced cytotoxicity via inhibiting PI3K/AKT but not the MAPK/ERK pathway. Conclusion: The trastuzumab/AT-101 combination may be a good candidate for patients with trastuzumab-resistant Her2-positive breast cancer and inhibition of the PI3K/AKT pathway may be one of the underlying mechanisms. © 2019 Gulcan Bulut, Harika Atmaca & Burcak Karaca.
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Keywords
Antineoplastic Agents, Immunological, Antineoplastic Agents, Phytogenic, Antineoplastic Combined Chemotherapy Protocols, Apoptosis, Breast Neoplasms, Cell Line, Tumor, Drug Screening Assays, Antitumor, Drug Synergism, Female, Gossypol, Humans, Phosphatidylinositol 3-Kinases, Proto-Oncogene Proteins c-akt, Receptor, ErbB-2, Signal Transduction, Trastuzumab, isosorbide, mitogen activated protein kinase, phosphatidylinositol 3 kinase, protein kinase B, trastuzumab, antineoplastic agent, epidermal growth factor receptor 2, ERBB2 protein, human, gossypol, gossypol acetic acid, immunological antineoplastic agent, phosphatidylinositol 3 kinase, protein kinase B, trastuzumab, apoptosis, Article, breast cancer, cancer cell, controlled study, cytotoxicity, drug effect, drug inhibition, drug mechanism, drug potentiation, human, human cell, MCF-10A cell line, MDA-MB-453 cell line, priority journal, signal transduction, SK-BR-3 cell line, apoptosis, breast tumor, drug screening, female, metabolism, pathology, tumor cell line