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

Abstract
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.
AuthorsKang-Sik Seo, Hoon Kim, Tae-Hwa Hong, Jong-Seok Kim, Kyoung-Sub Song, Eun-Jin Yun, Ji-Hoon Park, Young-Hoon Jung, Jong-Il Park, Gi Ryang Kweon, Wan-Hee Yoon, Kyu Lim, Byung-Doo Hwang
JournalBiochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 434 Issue 3 Pg. 634-40 (May 10 2013) ISSN: 1090-2104 [Electronic] United States
PMID23583412 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2013 Elsevier Inc. All rights reserved.
Chemical References
  • Apoptosis Inducing Factor
  • Bridged Bicyclo Compounds, Heterocyclic
  • Tubulin
  • apicularen A
Topics
  • Apoptosis (drug effects)
  • Apoptosis Inducing Factor (metabolism)
  • Blotting, Western
  • Bridged Bicyclo Compounds, Heterocyclic (pharmacology)
  • Cell Line, Tumor
  • Colonic Neoplasms (metabolism, pathology)
  • Down-Regulation (drug effects)
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Humans
  • Membrane Potential, Mitochondrial (drug effects)
  • Microtubules (drug effects, metabolism)
  • Protein Transport
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tubulin (metabolism)

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