Wortmannin induces MCF-7 breast cancer cell death via the apoptotic pathway, involving chromatin condensation, generation of reactive oxygen species, and membrane blebbing
Rozina Akter,1 Md. Zakir Hossain,2 Maurice G Kleve,3 Michael A Gealt3
1Applied Biosciences Emphasis, Department of Applied Science, 2Graduate Institute of Technology, 3Department of Biology, College of Science and of Mathematics, University Arkansas at Little Rock, Little Rock, AR, USA
Background: Apoptosis can be used as a reliable marker for evaluating potential chemotherapeutic agents. Because wortmannin is a microbial steroidal metabolite, it specifically inhibits the phosphatidyl inositol 3-kinase pathway, and could be used as a promising apoptosis-based therapeutic agent in the treatment of cancer. The objective of this study was to investigate the biomolecular mechanisms involved in wortmannin-induced cell death of breast cancer-derived MCF-7 cells.
Methods and results: Our experimental results demonstrate that wortmannin has strong apoptotic effects through a combination of different actions, including reduction of cell viability in a dose-dependent manner, inhibition of proliferation, and enhanced generation of intracellular reactive oxygen species.
Conclusion: Our findings suggest that wortmannin induces MCF-7 cell death via a programmed pathway showing chromatin condensation, nuclear fragmentation, reactive oxygen species, and membrane blebbing, which are characteristics typical of apoptosis.
Keywords: wortmannin, human breast adenocarcinoma, apoptosis, reactive oxygen species, flow cytometry
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