Trastuzumab in combination with AT-101 induces cytotoxicity and apoptosis in Her2 positive breast cancer cells.
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.
['Bulut|Gulcan|G|https://orcid.org/0000-0001-7382-0972', 'Atmaca|Harika|H|', 'Karaca|Burcak|B|']
D000074322:Antineoplastic Agents, Immunological D000972:Antineoplastic Agents, Phytogenic D000971:Antineoplastic Combined Chemotherapy Protocols D017209:Apoptosis D001943:Breast Neoplasms D045744:Cell Line, Tumor D004354:Drug Screening Assays, Antitumor D004357:Drug Synergism D005260:Female D006072:Gossypol D006801:Humans D019869:Phosphatidylinositol 3-Kinases D051057:Proto-Oncogene Proteins c-akt D018719:Receptor, ErbB-2 D015398:Signal Transduction D000068878:Trastuzumab
trastuzumab AT-101 apoptosis PI3K/AKT synergism