Trichodermin Induces G0/G1 Cell Cycle Arrest by Inhibiting c-Myc in Ovarian Cancer Cells and Tumor Xenograft-Bearing Mice
- PMID: 34065149
- PMCID: PMC8126000
- DOI: 10.3390/ijms22095022
Trichodermin Induces G0/G1 Cell Cycle Arrest by Inhibiting c-Myc in Ovarian Cancer Cells and Tumor Xenograft-Bearing Mice
Abstract
Ovarian cancer is a fatal gynecological cancer because of a lack of early diagnosis, which often relapses as chemoresistant. Trichodermin, a trichothecene first isolated from Trichoderma viride, is an inhibitor of eukaryotic protein synthesis. However, whether trichodermin is able to suppress ovarian cancer or not was unclear. In this study, trichodermin (0.5 µM or greater) significantly decreased the proliferation of two ovarian cancer cell lines A2780/CP70 and OVCAR-3. Normal ovarian IOSE 346 cells were much less susceptible to trichodermin than the cancer cell lines. Trichodermin predominantly inhibited ovarian cancer cells by inducing G0/G1 cell cycle arrest rather than apoptosis. Trichodermin decreased the expression of cyclin D1, CDK4, CDK2, retinoblastoma protein, Cdc25A, and c-Myc but showed little effect on the expression of p21Waf1/Cip1, p27Kip1, or p16Ink4a. c-Myc was a key target of trichodermin. Trichodermin regulated the expression of Cdc25A and its downstream proteins via c-Myc. Overexpression of c-Myc attenuated trichodermin's anti-ovarian cancer activity. In addition, trichodermin decelerated tumor growth in BALB/c nude mice, proving its effectiveness in vivo. These findings suggested that trichodermin has the potential to contribute to the treatment of ovarian cancer.
Keywords: A2780/CP70 cells; Cdc25A; OVCAR-3 cells; c-Myc; cell cycle arrest; trichodermin.
Conflict of interest statement
The authors declare no conflict of interest.
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References
-
- Targeted Cancer Therapies. [(accessed on 27 July 2020)]; Available online: https://www.cancer.gov/about-cancer/treatment/types/targeted-therapies/t....
-
- McDonald M.E., Salinas E.A., Devor E.J., Newtson A.M., Thiel K.W., Goodheart M.J., Bender D.P., Smith B.J., Leslie K.K., Gonzalez-Bosquet J. Molecular characterization of non-responders to chemotherapy in serous ovarian cancer. Int. J. Mol. Sci. 2019;20:1175. doi: 10.3390/ijms20051175. - DOI - PMC - PubMed
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