Viriditoxin Stabilizes Microtubule Polymers in SK-OV-3 Cells and Exhibits Antimitotic and Antimetastatic Potential
Autor: | Zhiran Ju, Jiafu Cao, Young-Suk Jung, Mingzhi Su, Eun La Kim, Chang-Hao Zhao, Jee H. Jung, Dan-Dan Li |
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Rok vydání: | 2020 |
Předmět: |
Mitosis
Pharmaceutical Science Apoptosis Naphthols macromolecular substances GTPase Antimitotic Agents Microtubules viriditoxin 01 natural sciences Article 03 medical and health sciences chemistry.chemical_compound antimetastatic Cell Movement Microtubule Drug Discovery Humans Cytotoxic T cell Neoplasm Invasiveness antimitotic FtsZ lcsh:QH301-705.5 Pharmacology Toxicology and Pharmaceutics (miscellaneous) Cell Proliferation 030304 developmental biology Ovarian Neoplasms 0303 health sciences biology 010405 organic chemistry SK-OV-3 0104 chemical sciences Cell biology G2 Phase Cell Cycle Checkpoints tubulin polymerization Tubulin lcsh:Biology (General) Paclitaxel chemistry Cell culture biology.protein Female microtubule |
Zdroj: | Marine Drugs Volume 18 Issue 9 Marine Drugs, Vol 18, Iss 445, p 445 (2020) |
ISSN: | 1660-3397 |
Popis: | Microtubules play a crucial role in mitosis and are attractive targets for cancer therapy. Recently, we isolated viriditoxin, a cytotoxic and antibacterial compound, from a marine fungus Paecilomyces variotii. Viriditoxin has been reported to inhibit the polymerization of bacterial FtsZ, a tubulin-like GTPase that plays an essential role in bacterial cell division. Given the close structural homology between FtsZ and tubulin, we investigated the potential antimitotic effects of viriditoxin on human cancer cells. Viriditoxin, like paclitaxel, enhanced tubulin polymerization and stabilized microtubule polymers, thereby perturbing mitosis in the SK-OV-3 cell line. However, the morphology of the stabilized microtubules was different from that induced by paclitaxel, indicating subtle differences in the mode of action of these compounds. Microtubule dynamics are also essential in cell movement, and viriditoxin repressed migration and colony formation ability of SK-OV-3 cells. Based on these results, we propose that viriditoxin interrupts microtubule dynamics, thus leading to antimitotic and antimetastatic activities. |
Databáze: | OpenAIRE |
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