Trastuzumab in combination with AT-101 induces cytotoxicity and apoptosis in Her2 positive breast cancer cells

Bulut G., ATMACA İLHAN H., Karaca B.

Future Oncology, vol.16, no.3, pp.4485-4495, 2019 (SCI-Expanded, Scopus) identifier identifier

  • Publication Type: Article / Article
  • Volume: 16 Issue: 3
  • Publication Date: 2019
  • Doi Number: 10.2217/fon-2019-0521
  • Journal Name: Future Oncology
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.4485-4495
  • Keywords: apoptosis, AT-101, PI3K/AKT, synergism, trastuzumab
  • Manisa Celal Bayar University Affiliated: Yes

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.