The potential effect of Tubulysin A on autophagy in a group of cancer cell lines

Abstract

Cancer continues to be a prominent global threat, and current chemotherapy options often involve tubulin-targeting compounds disrupting microtubule function. Autophagy's role in cancer varies across cell types, tumor stages, and carcinogenic stimuli. Recent attention has focused on autophagy as a response to antimitotic drugs. Our study spotlights TubA, a myxobacteria-derived peptide with potent antimitotic properties, demonstrating notable antiproliferative effects on diverse cancer cell lines at low concentrations. Remarkably, TubA proved more effective than TubB, another myxobacterial compound. In MCF-7 cells, TubA induced autophagy, increasing LC3-I lipidation to LC3-II and enhancing lysosomal activity and acidity. Intriguingly, TubA triggered an intrinsic apoptotic pathway mediated by autophagy, evidenced by increased cathepsin B activity, cytosolic leakage, and subsequent apoptosis through cytochrome c release. In summary, our findings indicate that TubA promotes cell death via cytotoxic autophagic activity in the MCF-7 cancer cell line.

Keywords

• Tubulysin A
• Autophagy
• Autophagic flux
• Apoptosis
• Caspase-3
• Microtubules