Synergistic anti-proliferative effects of combination of ABT-263 and MCL-1 selective inhibitor A-1210477 on cervical cancer cell lines

BMC Research Notes
Benedict Shi Xiang LianNethia Mohana-Kumaran

Abstract

There are number of studies which report that BCL-2 anti-apoptotic proteins (e.g. BCL-2, BCL-XL, and MCL-1) are highly expressed in cervical cancer tissues compared to the normal cervical epithelia. Despite these reports, targeting these proteins for cervical cancer treatment has not been explored extensively. BH3-mimetics that inhibit specific BCL-2 anti-apoptotic proteins may hold encouraging treatment outcomes for cervical cancer management. Hence, the aim of this pilot study is to investigate the sensitivity of cervical cancer cell lines to combination of two BH3-mimetics namely ABT-263 which selectively inhibits BCL-2, BCL-XL and BCL-w and A-1210477, a selective MCL-1 inhibitor. We report that combination of A-1210477 and ABT-263 exhibited synergistic effects on all cervical cancer cell lines tested. Drug sensitization studies revealed that A-1210477 sensitised the cervical cancer cell lines SiHa and CaSki to ABT-263 by 11- and fivefold, respectively. Sensitization also occurred in the opposite direction whereby ABT-263 sensitised SiHa and CaSki to A-1210477 by eightfold. This report shows that combination of ABT-263 and A-1210477 could be a potential treatment strategy for cervical cancer. Extensive drug mechanistic studi...Continue Reading

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Citations

Jul 28, 2020·Future Oncology·Siti Fairus Abdul RahmanNethia Mohana-Kumaran
Nov 21, 2020·Tropical Life Sciences Research·Benedict Lian Shi XiangNethia Mohana-Kumaran
Nov 17, 2020·GeroScience·Melod MehdipourIrina M Conboy
Feb 12, 2021·Cancer Management and Research·Rui YuShoujun Zhou
Feb 19, 2021·Biochimica Et Biophysica Acta. Molecular Cell Research·Sarah Kehr, Meike Vogler
Feb 26, 2021·Oncogene·Ethan L MorganAndrew Macdonald
Apr 23, 2021·Journal of Hematology & Oncology·Haolan WangYongheng Chen

Datasets Mentioned

BETA
ABT-263

Methods Mentioned

BETA
biopsies
xenograft

Related Concepts

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BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.