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

2021 ◽  
Vol 22 (9) ◽  
pp. 5022
Author(s):  
Ying Gao ◽  
Sarah L. Miles ◽  
Piyali Dasgupta ◽  
Gary O. Rankin ◽  
Stephen Cutler ◽  
...  

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.

2021 ◽  
Author(s):  
Portia P Raphela-Choma ◽  
Mthokozisi BC Simelane ◽  
Mpho S Choene

Abstract Background Natural compounds derived from various medicinal plants may activate several physiological pathways which can be valuable to diseases such as cancer. Isomukaadial acetate has previously been shown to possess antimalarial and anti-diabetic properties. The purpose of this study was to evaluate the antiproliferative effects of isomukaadial acetate on breast and ovarian cancer cell lines. Method Cell viability assays were conducted using AlamarBlue assay and xCELLigence system. Cell apoptosis and cell cycle arrest were determined and analyzed by flow cytometer. Effector caspase (3/7) activation was evaluated by caspase Glo®-3/7 reagent and gene expression was analyzed by Real-Time Polymerase Chain Reaction. Results The Alamar blue assay and xCELLigence showed that Iso-mukaadial acetate exhibited anti-proliferative effects on MDA-MB 231, RMG-1, and HEK 293 cell lines in a concentration-dependent manner. Iso-mukaadial acetate induced apoptosis in both cancer cell lines caused cell cycle arrest at the S phase (RMG-1) and early G2 phase (MDA-MB 231) and expressed caspase 3/7 activity in MDA-MB 231 and RMG-1 cells. BAX and p21 were upregulated in MDA-MB 231 and RMG-1 cells after treatment. Conclusion IMA significantly inhibited cancer growth and induced cell apoptosis with cell cycle modulation. IMA may be considered a promising candidate for the development of anticancer drugs either for its cytotoxic or cytostatic effect Furthermore, IMA requires to be further studied more to clearly understand its mechanism of action on cancer cells.


2021 ◽  
Author(s):  
Portia Raphela-Choma ◽  
Mthokozisi Simelane ◽  
Mpho Choene

Abstract Background Natural compounds derived from various medicinal plants may activate several physiological pathways which can be valuable to diseases such as cancer. Isomukaadial acetate has previously been shown to possess antimalarial and anti-diabetic properties. The purpose of this study was to evaluate the antiproliferative effects of isomukaadial acetate on breast and ovarian cancer cell lines. Method Cell viability assays were conducted using AlamarBlue assay and xCELLigence system. Cell apoptosis and cell cycle arrest were determined and analyzed by flow cytometer. Effector caspase (3/7) activation was evaluated by caspase Glo®-3/7 reagent and gene expression was analyzed by Real-Time Polymerase Chain Reaction. Results The Alamar blue assay and xCELLigence showed that Iso-mukaadial acetate exhibited anti-proliferative effects on MDA-MB 231, RMG-1, and HEK 293 cell lines in a concentration-dependent manner. Iso-mukaadial acetate induced apoptosis in both cancer cell lines caused cell cycle arrest at the S phase (RMG-1) and early G2 phase (MDA-MB 231) and expressed caspase 3/7 activity in MDA-MB 231 and RMG-1 cells. BAX and p21 were upregulated in MDA-MB 231 and RMG-1 cells after treatment. Conclusion IMA significantly inhibited cancer growth and induced cell apoptosis with cell cycle modulation. IMA may be considered a promising candidate for the development of anticancer drugs either for its cytotoxic or cytostatic effect Furthermore, IMA requires to be further studied more to clearly understand its mechanism of action on cancer cells.


Gene ◽  
2013 ◽  
Vol 512 (1) ◽  
pp. 127-133 ◽  
Author(s):  
Chen Wu ◽  
Xiaobo Liu ◽  
Yuanyuan Wang ◽  
Huanna Tian ◽  
Yuanyuan Xie ◽  
...  

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