Abstract | PURPOSE:
Apicularen A has been shown to cause growth inhibition and apoptosis in several cancer cell lines. However, the mechanisms of apicularen A-induced cell death and in vivo effects remain unclear. In this study, we investigated the molecular mechanisms of apicularen A-induced cell death in HM7 human colon cancer cells in vitro and anticancer activity in vivo. EXPERIMENTAL DESIGN: We tested cytotoxicity with a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, apoptosis with DNA fragmentation assay, mitochondrial membrane potential, and cell cycle with fluorescence-activated cell sorting. Caspase activation was done by fluorometry. Alterations of microtubule structure, tubulin protein, and mRNA level were assessed by immunofluorescence, Western blot, and reverse transcription-PCR. In vivo studies were assessed using nude mice tumor cell growth in xenograft model and liver colonization assay. RESULTS: CONCLUSION:
Apicularen A induces cell death of HM7 cells through up-regulating Fas ligand and disruption of microtubule architecture with down-regulation of tubulin level. These findings indicate that apicularen A is a promising new microtubule-targeting compound.
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Authors | Jong-Seok Kim, Young-Chul Lee, Ho-Tak Nam, Ge Li, Eun-Jin Yun, Kyoung-Sub Song, Kang-Sik Seo, Ji-Hoon Park, Jong-Woong Ahn, Okpyo Zee, Jong-Il Park, Wan-Hee Yoon, Kyu Lim, Byung-Doo Hwang |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 13
Issue 21
Pg. 6509-17
(Nov 01 2007)
ISSN: 1078-0432 [Print] United States |
PMID | 17975164
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Bridged Bicyclo Compounds, Heterocyclic
- Fas Ligand Protein
- Tubulin
- apicularen A
- Caspase 3
- Caspase 8
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Topics |
- Animals
- Bridged Bicyclo Compounds, Heterocyclic
(pharmacology)
- Caspase 3
(metabolism)
- Caspase 8
(metabolism)
- Cell Death
- Cell Line, Tumor
- Colonic Neoplasms
(metabolism, pathology)
- DNA Fragmentation
- Enzyme Activation
- Fas Ligand Protein
(metabolism)
- Gene Expression Regulation
- Gene Expression Regulation, Neoplastic
- Humans
- Liver
(metabolism)
- Membrane Potential, Mitochondrial
- Mice
- Mice, Nude
- Microtubules
(metabolism)
- Tubulin
(metabolism)
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