Ling Huang1
,
Xin-Bao Wang1,
Qi-Ming Yu1,
Qing-Ying Luo2,
Zun-Zhen Zhang2
1Department of Abdominal Surgery, Zhejiang Cancer Hospital, Hangzhou 310022;
2Department of Environmental Health, West China School of Public Health, Sichuan University, Chengdu 610041, China.
For correspondence:- Ling Huang
Email: zhangzunzhen819@gmail.com Tel:+8657188122233
Received: 29 December 2014
Accepted: 27 June 2015
Published: 30 August 2015
Citation:
Huang L, Wang X, Yu Q, Luo Q, Zhang Z.
Synergistic cancer growth-inhibitory effect of emodin and low-dose cisplatin on gastric cancer cells in vitro. Trop J Pharm Res 2015; 14(8):1427-1434
doi:
10.4314/tjpr.v14i8.15
© 2015 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..
Abstract
Purpose: To investigate the anti-cancer activity of emodin and its combination with low-dose cisplatin against human gastric cancer (SNU-5), including their effects on cell cycle phase distribution, apoptosis and cancer cell morphology.
Methods: The anti-cancer activity of emodin, cisplatin and their combination against human gastric cancer (SNU-5) cells was evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5 diphenyltetra -zolium bromide (MTT) assay. Flow cytometry, using propidium iodide as a staining agent, was employed to study their effect on cell cycle phase distribution. Apoptosis induced by emodin and cisplatin was evaluated by annexin V binding assay using a flow cytometer. Alterations in cell morphology following apoptosis were studied by both fluorescence and transmission electron microscopy.
Results: Emodin induced a dose-dependent growth inhibitory effect on human gastric cancer cells in vitro. Furthermore, the combination of 25 µM emodin + 3.0µM cisplatin induced relatively higher inhibitory effect (98 %) on these cells, indicating a synergistic enhancement of the anticancer activity of cisplatin. The combined effect of emodin and cisplatin also resulted in significant apoptosis induction as well as cell cycle arrest in comparison to the individual treatment by emodin (G2/M population of 14.82 %) or cisplatin (G2/M population - 36.20 %) Fluorescence and transmission electron microscopy also revealed that combination of emodin with cisplatin resulted in promounced apoptosis induction as well as cell morphology alterations. The percentage of early as well as late apoptotic cells was higher for the combination treatment than for the individual treatment by emodin or cisplatin.
Conclusion:Emodin synergistically enhances the anti-cancer activity of cisplatin in human gastric cancer (SNU-5) cells by inducing apoptosis as well as cell cycle arrest, thus paving way for improved chemotherapy in cancer.
Keywords: Gastric cancer, Emodin, CisplatinApoptosis, Flow cytometry, Cell cycle arrest