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Article

Trichodermin Induces G0/G1 Cell Cycle Arrest by Inhibiting c-Myc in Ovarian Cancer Cells and Tumor Xenograft-Bearing Mice

1
Tea Research Institute, Chinese Academy of Agricultural Sciences, Hangzhou 310008, China
2
Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, USA
3
College of Pharmacy, University of South Carolina, CLS Columbia, Columbia, SC 29208, USA
4
College of Health, Science, Technology and Mathematics, Alderson Broaddus University, Philippi, WV 26416, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Siyaram Pandey
Int. J. Mol. Sci. 2021, 22(9), 5022; https://doi.org/10.3390/ijms22095022
Received: 1 April 2021 / Revised: 20 April 2021 / Accepted: 6 May 2021 / Published: 9 May 2021
(This article belongs to the Special Issue Natural Compounds with Cancer-Selective Toxicity)
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. View Full-Text
Keywords: trichodermin; A2780/CP70 cells; OVCAR-3 cells; c-Myc; cell cycle arrest; Cdc25A trichodermin; A2780/CP70 cells; OVCAR-3 cells; c-Myc; cell cycle arrest; Cdc25A
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MDPI and ACS Style

Gao, Y.; Miles, S.L.; Dasgupta, P.; Rankin, G.O.; Cutler, S.; Chen, Y.C. Trichodermin Induces G0/G1 Cell Cycle Arrest by Inhibiting c-Myc in Ovarian Cancer Cells and Tumor Xenograft-Bearing Mice. Int. J. Mol. Sci. 2021, 22, 5022. https://doi.org/10.3390/ijms22095022

AMA Style

Gao Y, Miles SL, Dasgupta P, Rankin GO, Cutler S, Chen YC. Trichodermin Induces G0/G1 Cell Cycle Arrest by Inhibiting c-Myc in Ovarian Cancer Cells and Tumor Xenograft-Bearing Mice. International Journal of Molecular Sciences. 2021; 22(9):5022. https://doi.org/10.3390/ijms22095022

Chicago/Turabian Style

Gao, Ying, Sarah L. Miles, Piyali Dasgupta, Gary O. Rankin, Stephen Cutler, and Yi C. Chen 2021. "Trichodermin Induces G0/G1 Cell Cycle Arrest by Inhibiting c-Myc in Ovarian Cancer Cells and Tumor Xenograft-Bearing Mice" International Journal of Molecular Sciences 22, no. 9: 5022. https://doi.org/10.3390/ijms22095022

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