Anti-proliferative activity and cell cycle arrest induced by evodiamine on paclitaxel-sensitive and -resistant human ovarian cancer cells

Zhang Feng Zhong, Wen Tan, Sheng Peng Wang, Wen An Qiang, Yi Tao Wang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

Chemo-resistance is the main factor for poor prognosis in human ovarian epithelial cancer. Active constituents derived from Chinese medicine with anti-cancer potential might circumvent this obstacle. In our present study, evodiamine (EVO) derived from Evodia rutaecarpa (Juss.) Benth suppressed the proliferation of human epithelial ovarian cancer, A2780 and the related paclitaxel-resistant cell lines and did not cause cytotoxicity, as confirmed by the significant decline of clone formation and the representative alterations of CFDA-SE fluorescence. Meanwhile, EVO induced cell cycle arrest in a dose- and time-dependent manner. This disturbance might be mediated by the cooperation of Cyclin B1 and Cdc2, including the up-regulation of Cyclin B1, p27, and p21, and activation failure of Cdc2 and pRb. MAPK signaling pathway regulation also assisted in this process. Furthermore, chemo-sensitivity potential was enhanced as indicated in A2780/PTX R cells by the down-regulation of MDR-1 expression, accompanied by MDR-1 function suppression. Taken together, we confirmed initially that EVO exerted an anti-proliferative effect on human epithelial ovarian cancer cells, A2780/WT and A2780/PTX R, induced G2/M phase cell cycle arrest, and improved chemo-resistance. Overall, we found that EVO significantly suppressed malignant proliferation in human epithelial ovarian cancer, thus proving to be a potential anti-cancer agent in the future.

Original languageEnglish (US)
Article number16415
JournalScientific reports
Volume5
DOIs
StatePublished - Nov 10 2015

Funding

This study was supported by the Macao Science and Technology Development Fund (077/2011/A3 and 048/2013/A2), and the Research Fund of University of Macau (CPG2014-00012-ICMS, UL016/09Y4/ CMS/WYT01/ICMS and MYRG208 (Y3-L4)-ICMS11-WYT). W.A. Qiang was partially supported by the Baskes Foundation and Robert H. Lurie Comprehensive Cancer Center at the Northwestern University. We also thank Stacy Ann Kujawa in Northwestern University Feinberg School of Medicine for critical proofreading of the manuscript.

ASJC Scopus subject areas

  • General

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