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Viriditoxin Stabilizes Microtubule Polymers in SK-OV-3 Cells and Exhibits Antimitotic and Antimetastatic Potential.

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.

SUBMITTER: Su M

PROVIDER: S-EPMC7551567 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Viriditoxin Stabilizes Microtubule Polymers in SK-OV-3 Cells and Exhibits Antimitotic and Antimetastatic Potential.

Su Mingzhi M Zhao Changhao C Li Dandan D Cao Jiafu J Ju Zhiran Z Kim Eun La E Jung Young-Suk YS Jung Jee H JH

Marine drugs 20200827 9

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 <i>Paecilomyces variotii</i>. 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 viriditoxi ...[more]

PMID: 32867174

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Project description:Chondrosarcoma is primary bone cancer, with the forceful capacity to cause local invasion and distant metastasis, and has a poor prognosis. Cancer metastasis is a complication of most cancers; it is one of the leading causes of cancer-related death. Rhodomyrtone is a pure compound that has been shown to induce apoptosis and antimetastasis in skin cancer. However, the inhibitory effect of rhodomyrtone on human chondrosarcoma cell metastasis is largely unknown. Effect of rhodomyrtone on cell viability in SW1353 cell was determined by MTT assay. Antimigration, anti-invasion, and antiadhesion were carried out to investigate the antimetastatic potential of rhodomyrtone on SW1353 cells. Gelatin zymography was performed to determine matrix metalloproteinase-2 (MMP-2) and MMP-9 activities. The effect of rhodomyrtone on the underlying mechanisms was performed by Western blot analysis. The results demonstrated that rhodomyrtone reduced cell viability of SW1353 cells at the low concentration (<3??g/mL); cell viability was >80%. Rhodomyrtone at the subcytotoxic concentrations (0.5, 1.5, and 3??g/mL) significantly inhibited cell migration, invasion, and adhesion of SW1353 cells in a dose-dependent fashion. Protein expression of integrin ?v, integrin ?3, and the downstream migratory proteins including focal adhesion kinase (FAK) and the phosphorylation of serine/threonine AKT, Ras, RhoA, Rac1, and Cdc42 were inhibited after treatment with rhodomyrtone. Moreover, we found that rhodomyrtone decreased the protein level of MMP-2 and MMP-9 as well as the enzyme activity in SW1353 cells. Meanwhile, tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2 expression was increased in a dose-dependent fashion. Besides, rhodomyrtone dramatically inhibited the expression of growth factor receptor-bound protein-2 (GRB2) and the phosphorylated form of extracellular signal regulation kinase1/2 (ERK1/2) and c-Jun N-terminal kinase1/2 (JNK1/2). These results indicated that rhodomyrtone inhibited SW1353 cell migration, invasion, and metastasis by suppressing integrin ?v?3/FAK/AKT/small Rho GTPases pathway as well as downregulation of MMP-2/9 via ERK and JNK signal inhibition. These findings indicate that rhodomyrtone possessed the antimetastasis activity that may be used for antimetastasis therapy in the future.

Dataset Information

Viriditoxin Stabilizes Microtubule Polymers in SK-OV-3 Cells and Exhibits Antimitotic and Antimetastatic Potential.

Publications

Viriditoxin Stabilizes Microtubule Polymers in SK-OV-3 Cells and Exhibits Antimitotic and Antimetastatic Potential.

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