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

• Published in: Biochemical and biophysical research communications 2013-05, Vol.434 (3), p.634-640
• Main Authors: Seo, Kang-Sik, Kim, Hoon, Hong, Tae-Hwa, Kim, Jong-Seok, Song, Kyoung-Sub, Yun, Eun-Jin, Park, Ji-Hoon, Jung, Young-Hoon, Park, Jong-Il, Kweon, Gi Ryang, Yoon, Wan-Hee, Lim, Kyu, Hwang, Byung-Doo
• Format: Article
• Language: English
• Subjects: Apicularen A acetate; Apoptosis - drug effects; Apoptosis Inducing Factor - metabolism; Apoptosis-inducing factor; Blotting, Western; Bridged Bicyclo Compounds, Heterocyclic - pharmacology; Caspase-independent apoptosis; Cell Line, Tumor; Colonic Neoplasms - metabolism; Colonic Neoplasms - pathology; Down-Regulation - drug effects; Flow Cytometry; Fluorescent Antibody Technique; Humans; Membrane Potential, Mitochondrial - drug effects; Microtubule disruption; Microtubules - drug effects; Microtubules - metabolism; Protein Transport; Reverse Transcriptase Polymerase Chain Reaction; Tubulin - metabolism
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2013.03.133

•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.