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.

Highlights

  • Gastric cancer is the second leading cause of cancer-related deaths worldwide after lung cancer [1,2]

  • The objective of the present study was to evaluate the effect of combining emodin, a natural compound extracted from various Rheum medicinal plant species, with cisplatin on human gastric carcinoma cell line (SNU-5) in vitro

  • Emodin was reported to be cytotoxic to FM3A, a mouse mammary carcinoma cell line [14]

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Summary

Introduction

Gastric cancer (stomach cancer) is the second leading cause of cancer-related deaths worldwide after lung cancer [1,2]. Gastric cancer is the third leading cause of cancer mortality in China. Various advances have arisen in gastric cancer management, patient prognosis remains very poor. Chemotherapy remains the backbone of treatments of gastric cancer and cisplatin is one of the most extensively used first line chemotherapeutic agents for gastric cancer [4]. These therapeutic strategies are insufficient due to severe side effects experienced by patients and drug resistance. It is important to find novel agents that can be used to enhance the anti-cancer effects of common chemotherapeutic drugs currently being used for gastric cancer treatment [4,5]

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