Viriditoxin Induces G2/M Cell Cycle Arrest and Apoptosis in A549 Human Lung Cancer Cells.
10.20307/nps.2015.21.4.282
- Author:
Ju Hee PARK
1
;
Tae Hwan NOH
;
Haibo WANG
;
Nam Deuk KIM
;
Jee H JUNG
Author Information
1. College of Pharmacy, Pusan National University, Busan 609-735, Korea. jhjung@pusan.ac.kr
- Publication Type:Original Article
- Keywords:
Viriditoxin;
Paecilomyces variotii;
FtsZ;
Tubulin;
G2/M cell cycle arrest;
Apoptosis;
A549 cells
- MeSH:
Apoptosis*;
Cell Cycle Checkpoints*;
Cell Cycle*;
Cell Death;
Cell Division;
Eukaryotic Cells;
GTP Phosphohydrolases;
Humans*;
Hydrogen;
Lung Neoplasms*;
Lung*;
Paclitaxel;
Paecilomyces;
Polymerization;
Polymers;
Tubulin
- From:Natural Product Sciences
2015;21(4):282-288
- CountryRepublic 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.
