Protuboxepin A, a marine fungal metabolite, inducing metaphase arrest and chromosomal misalignment in tumor cells

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Title
Protuboxepin A, a marine fungal metabolite, inducing metaphase arrest and chromosomal misalignment in tumor cells
Author(s)
Y Asami; Jae-Hyuk JangNak Kyun Soung; L He; D O Moon; Jong Won Kim; H Oh; M Muroi; H Osada; Bo Yeon KimJong Seog Ahn
Bibliographic Citation
Bioorganic & Medicinal Chemistry, vol. 20, no. 12, pp. 3799-3806
Publication Year
2012
Abstract
Previously we reported the identification of a new oxepin-containing diketopiperazine-type marine fungal metabolite, named protuboxepin A which showed antiproliferative activity in several cancer cell lines. In this study we elucidated the mechanism by which protuboxepin A induces cancer cell growth inhibition. Here we report that protuboxepin A induced round-up morphology, M phase arrest, and an increase in the subG 1 population in tumor cells in a dose dependent manner. Our investigations revealed that protuboxepin A directly binds to α,β-tubulin and stabilizes tubulin polymerization thus disrupting microtubule dynamics. This disruption leads to chromosome misalignment and metaphase arrest which induces apoptosis in cancer. Overall, we identified protuboxepin A as a microtubule-stabilizing agent which has a distinctly different chemical structure from previously reported microtubule inhibitors. These results indicate that protuboxepin A has a potential of being a new and effective anti-cancer drug.
Keyword
Chromosomal misalignmentMarine fungal metaboliteMetaphase arrestProtuboxepin ATubulin
ISSN
0968-0896
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.bmc.2012.04.039
Type
Article
Appears in Collections:
Ochang Branch Institute > Chemical Biology Research Center > 1. Journal Articles
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