Protuboxepin A, a marine fungal metabolite, inducing metaphase arrest and chromosomal misalignment in tumor cells
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- Protuboxepin A, a marine fungal metabolite, inducing metaphase arrest and chromosomal misalignment in tumor cells
- Y Asami; Jae-Hyuk Jang; Nak Kyun Soung; L He; D O Moon; Jong Won Kim; H Oh; M Muroi; H Osada; Bo Yeon Kim; Jong Seog Ahn
- Bibliographic Citation
- Bioorganic & Medicinal Chemistry, vol. 20, no. 12, pp. 3799-3806
- Publication Year
- 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.
- Chromosomal misalignmentMarine fungal metaboliteMetaphase arrestProtuboxepin ATubulin
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- Ochang Branch Institute > Chemical Biology Research Center > 1. Journal Articles
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