Natural Product Sciences  2015;21(4):282-288

doi:10.20307/nps.2015.21.4.282

Viriditoxin Induces G2/M Cell Cycle Arrest and Apoptosis in A549 Human Lung Cancer Cells.

Ju Hee PARK 1 ; Tae Hwan NOH ; Haibo WANG ; Nam Deuk KIM ; Jee H JUNG

Affiliations

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Keywords

Viriditoxin; Paecilomyces variotii; FtsZ; Tubulin; G2/M cell cycle arrest; Apoptosis; A549 cells

Country

Republic of Korea

Language

English

Abstract

Viriditoxin is a fungal metabolite isolated from Paecilomyces variotii, which was derived from the giant jellyfish Nemopilema nomurai. Viriditoxin was reported to inhibit polymerization of FtsZ, which is a key protein for bacterial cell division and a structural homologue of eukaryotic tubulin. Both tubulin and FtsZ contain a GTP-binding domain, have GTPase activity, assemble into protofilaments, two-dimensional sheets, and protofilament rings, and share substantial structural identities. Accordingly, we hypothesized that viriditoxin may inhibit eukaryotic cell division by inhibiting tubulin polymerization as in the case of bacterial FtsZ inhibition. Docking simulation of viriditoxin to beta-tubulin indicated that it binds to the paclitaxel-binding domain and makes hydrogen bonds with Thr276 and Gly370 in the same manner as paclitaxel. Viriditoxin suppressed growth of A549 human lung cancer cells, and inhibited cell division with G2/M cell cycle arrest, leading to apoptotic cell death.