Apicularen A acetate induces cell death via AIF translocation and disrupts the microtubule network by down-regulating tubulin in HM7 human colon cancer cells

•We synthesized the acetyl derivative of the antitumor agent apicularen A.•Apicularen A acetate induces cytotoxicity and sub-G1 accumulation in HM7 cells.•Apicularen A acetate triggers caspase-independent cell death via AIF translocation.•Apicularen A acetate disrupts the microtubule networks by tubulin down-regulation.•Substitution of functional groups of drugs may be a good strategy for cancer therapy. Apicularen A is a novel antitumor agent and strongly induces death in tumor cells. In this study, we synthesized apicularen A acetate, an acetyl derivative of apicularen A, and investigated its antitumor effect and mechanism in HM7 colon cancer cells. Apicularen A acetate induced apoptotic cell death and caspase-3 activation; however, the pan-caspase inhibitor Z-VAD-fmk could not prevent this cell death. Apicularen A acetate induced the loss of mitochondrial membrane potential and the translocation of apoptosis-inducing factor (AIF) from mitochondria. In addition, apicularen A acetate significantly decreased tubulin mRNA and protein levels and induced disruption of microtubule networks. Taken together, these results indicate that the mechanism of apicularen A acetate involves caspase-independent apoptotic cell death and disruption of microtubule architecture.