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Euphornin reduces proliferation of human cervical adenocarcinoma HeLa cells through induction of apoptosis and G2/M cell cycle arrest

Authors Li XQ, Bai YL, Zhang DL, Jiao HS, He RX

Received 20 February 2018

Accepted for publication 12 May 2018

Published 27 July 2018 Volume 2018:11 Pages 4395—4405

DOI https://doi.org/10.2147/OTT.S166018

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Andrew Yee

Peer reviewer comments 4

Editor who approved publication: Dr Yao Dai


Xiao-Qiang Li,1,* Yin-Liang Bai,1,* De-Li Zhang,1,* Hai-Sheng Jiao,1 Rong-Xia He2

1Pharmacy Department, Lanzhou University Second Hospital, Lanzhou 730030, China; 2Department of Gynecology, Lanzhou University Second Hospital, Lanzhou 730030, China

*These authors contributed equally to this work

Background: The plant Euphorbia helioscopia L. has been used in traditional Chinese medicine for treating various disorders such as tuberculosis and edema. The aim of this study was to investigate the effect of euphornin, a bioactive compound isolated from E. helioscopia, on proliferation of human cervical adenocarcinoma HeLa cells by analyzing cell viability, rate of apoptosis, and cell cycle progression.
Materials and methods: The sulforhodamine B assay was used to study the effect of euphornin on the proliferation of HeLa cells. Morphological changes to cell nuclei were identified after Hoechst 33342 staining. Mitochondrial membrane depolarization (MMP) was analyzed after staining with JC-1 dye. The influence of euphornin on the apoptosis rate was analyzed by Annexin V/propidium iodide double staining. Fluorescence-activated cell sorting was applied to investigate the influence of euphornin on cell cycle progression. Proteins were obtained from HeLa cells and analyzed by Western blots.
Results: A cell viability assay showed that euphornin inhibited proliferation of HeLa cells in a dose-dependent and time-dependent manner. Euphornin also induced apoptosis in a concentration-dependent manner, with the rates of apoptosis ranging from 25.3% to 52.6%. A high concentration of euphornin was found to block HeLa cells at the G2/M stage. A Western blot analysis suggested that euphornin might exhibit antitumor activity by inducing apoptosis. Euphornin treatment altered the ratio of Bax/Bcl-2 in HeLa cells, which led to the release of cytochrome complex. The levels of cleaved caspase-3, caspase-8, caspase-9, and caspase-10 were also markedly increased by euphornin treatment. Analysis of cell cycles indicated that euphornin induced cell cycle arrest by increasing the level of the phospho-CDK1 (Tyr15) protein. The various assays demonstrated that euphornin treatment resulted in a significant suppression of cell growth accompanied by G2/M cell cycle arrest and increased rate of apoptosis via mitochondrial and caspase pathways.
Conclusion: Our findings suggest that euphornin has the potential to be used as a cancer therapeutic agent against human cervical adenocarcinoma.

Keywords: euphornin, cervical adenocarcinoma HeLa cells, proliferation, apoptosis, G2/M cell cycle arrest

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