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

作者：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

来源：Biochemical and Biophysical Research Communications, 2013, 434(3): 634-640.

DOI：10.1016/j.bbrc.2013.03.133

• Apicularen A acetate
• Caspase-independent apoptosis
• Apoptosis-inducing factor
• Microtubule disruption

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.

• 出版日期2013-5-10