Protuboxepin A

Producing organism
Aspergillus sp.
Biological activity
microtubule-stabilizing agent
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.
  • Lee SU, Asami Y, Lee D, Jang JH, Ahn JS, Oh H.: Protuboxepins A and B and protubonines A and B from the marine-derived fungus Aspergillus sp. SF-5044.
    J Nat Prod, 74(5): 1284-1287 (2011) PMID: 21366228 [ doi: 10.1021/np100880b ]
  • Asami Y, Jang JH, Soung NK, He L, Moon DO, Kim JW, Oh H, Muroi M, Osada H, Kim BY, Ahn JS.: Protuboxepin A, a marine fungal metabolite, inducing metaphase arrest and chromosomal misalignment in tumor cells.
    Bioorg Med Chem, 20(12): 3799-3806 (2012) PMID: 22595423 [ doi: 10.1016/j.bmc.2012.04.039 ]
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