Abstract
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.
Highlights
Several anticancer drugs are clinically available, drug therapies for cancer patients are still unsatisfactory owing to the associated undesirable side effects, emergence of drug resistance, and metastasis of cancer cells
The other reason for its selection was that SK-OV-3 is a drug-resistant cancer cell line
Our data showed that viriditoxin inhibited the proliferation of SK-OV-3 cells
Summary
Several anticancer drugs are clinically available, drug therapies for cancer patients are still unsatisfactory owing to the associated undesirable side effects, emergence of drug resistance, and metastasis of cancer cells. The development of alternative chemotherapeutic agents with enhanced therapeutic profile is required. Microtubules play a crucial role in mitosis and are recognized as one of the most attractive targets for anticancer drug development [1]. Cancer cells are sensitive to mitotic arrest and often undergo cell death in response to agents that perturb microtubule dynamics. Α- and β-tubulins form a heterodimer that polymerizes into microtubules. Microtubules are the major cytoskeletal components of eukaryotic cells and are involved in multiple cellular processes. Tubulins are polymerized into cytoskeletal microtubules to maintain cell shape, polarity, motility, and intracellular transport. During metaphase and anaphase, microtubules are disintegrated into tubulin monomers to be reassembled into microtubules to form mitotic spindles, which are required for chromosome segregation and cell division [4]
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