Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 22, Issue 9, Pages -Publisher
MDPI
DOI: 10.3390/ijms22095022
Keywords
trichodermin; A2780; CP70 cells; OVCAR-3 cells; c-Myc; cell cycle arrest; Cdc25A
Funding
- NIH from the National Center for Research Resources [P20RR016477]
- NIH from the National Institute for General Medical Sciences (NIGMS) [P20GM103434]
- NIGMS, a component of the National Institutes of Health (NIH) [P20GM104932]
- COBRE [GM102488/RR032138]
- FORTESSA [OD016165]
- ARIA [RR020866]
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Trichodermin effectively inhibits the proliferation of ovarian cancer cells by inducing G0/G1 cell cycle arrest, mainly targeting c-Myc. Its anti-tumor activity was also validated in animal experiments.
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 mu M 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 p21(Waf1/Cip1), p27(Kip1), or p16(Ink4a). 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.
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