Yukihiro Asami, Jae-Hyuk Jang, Nak-Kyun Soung, Long He, Dong Oh Moon, Jong Won Kim, Hyuncheol Oh, Makoto Muroi, Hiroyuki Osada, Bo Yeon Kim, Jong Seog Ahn
Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 30 Yeongudanji-ro, Ochang, Cheongwon, Chungbuk 363-883, Republic of Korea; Chemical Biology Department, RIKEN Advanced Science Institute, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
Bioorganic & medicinal chemistry 2012 Jun 15Previously 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. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.
Yukihiro Asami, Jae-Hyuk Jang, Nak-Kyun Soung, Long He, Dong Oh Moon, Jong Won Kim, Hyuncheol Oh, Makoto Muroi, Hiroyuki Osada, Bo Yeon Kim, Jong Seog Ahn. Protuboxepin A, a marine fungal metabolite, inducing metaphase arrest and chromosomal misalignment in tumor cells. Bioorganic & medicinal chemistry. 2012 Jun 15;20(12):3799-806
PMID: 22595423
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