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Title 

Ginkgetin induces G2-phase arrest in HCT116 colon cancer cells through the modulation of b-Myb and miRNA34a expression

 

Ginkgetin의 항암 효과 및 기전 규명

Authors 

Yu Jin LeeYeong-Rim KangSo Young LeeYena JinDong Cho HanByoung-Mog Kwon

Publisher 

Spandidos Publications

Issue Date 

2017

Citation 

International Journal of Oncology

Abstract 

Ginkgetin has been reported to display antitumor activity. However, the relevant pathway integrating cell cycle regulation and signaling pathways involved in growth inhibition in CRC cells remains to be identified. In this study, ginkgetin-treated HCT116 CRC cells exhibited significant dose-dependent growth inhibition with a GI50 value of 4.0 ?M for 48-h treatment, together with apoptosis, via G2-phase cell cycle arrest. When HCT116 cells were treated with 10 ginkgetin for 48 h, the percentage of cells in G2/M phase increased by 2.2-fold (43.25%) versus the untreated control (19.69%). Ginkgetin regulated the expression of genes that are critically involved in G2 phase arrest cells, such as b.Myb, CDC2 and cyclin B1. Furthermore, we found that the suppression of b.Myb expression by ginkgetin was rescued ∼5.1-fold by treatment with a miR-34a inhibitor (500 nM) and b.Myb was downregulated by >80% by 100 nM miR.34a mimic. These data suggest that the miRNA34a/b.Myb/cyclin B1 cascade plays a critical role in ginkgetin-induced G2 cell cycle arrest, as well as in the inhibition of HCT116 cell proliferation. Moreover, the administration of ginkgetin (10 mg/kg) reduced tumor volumes by 36.5% and tumor weight by 37.6% in the mice xenografted with HCT116 cells relative to their vehicle-treated counterparts. Therefore, ginkgetin is the first compound shown to regulate b.Myb by modulating miR-34a, and we suggest the use of ginkgetin as an inducer of G2 arrest for the treatment of CRC.

ISSN 

1019-6439

Link 

http://dx.doi.org/10.3892/ijo.2017.4116

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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