Antimycin induces apoptosis in rapamycin resistant SW620 colorectal cancer cells

Abstract

Mammalian target of rapamycin, (mTOR), a serine/threonine protein kinase is a central regulator of cell growth and proliferation and is observed to be hyperactive in many common cancers. Rapamycin, a natural macrolide immunosuppressant, forms a complex with FKBP12 and mTOR inhibiting mTOR activity. Classified as Duke's Type C level cancer, SW620s are colorectal, rapamycin resistant, adenocarcinoma cells with widespread metastasis. During a high through put screening of the National Cancer Institute's Mechanistic Diversity Set, we demonstrated that antimycin not only inhibits growth and proliferation but induces apoptosis in SW620 cells. Antimycin, a group of secondary metabolites produced by Streptomyces bacteria, disrupts the proton gradient across the inner mitochondrial membrane which results in the build‐up of the toxic, free radical superoxide. As a result, apoptosis was induced in several other colorectal cancer cell lines suggesting antimycin is a compound that could potentially be used for the treatment of colorectal cancer.