Abstract

Numerous studies have demonstrated that podophyllotoxin and its derivatives exhibit antitumor effects. The aim of the present study was to investigate SGC-7901 cell apoptosis and the underlying mechanism induced by podophyllotoxin. SGC-7901 cells were treated with varying concentrations of podophyllotoxin. MTT assays and flow cytometry were used to evaluate the effects of podophyllotoxin on the proliferation and apoptosis of SGC-7901 cells, while fluorescence inverted microscopy was used to observe the morphology of SGC-7901 cells that had been dyed with Hoechst 33258. In addition, laser scanning confocal microscopy was used to analyze the mitochondrial membrane potential (MMP) of SGC-7901 cells dyed with Rhodamine 123. Western blotting was performed to analyze the expression levels of cytochrome c (cyt-c), caspase-9 and caspase-3 in the SGC-7901 cells. The results indicated that podophyllotoxin was capable of inhibiting growth and inducing the apoptosis of SGC-7901 cells in a dose-dependent manner, causing cell cycle arrest at the G2/M phase. After 48 h of treatment, the apoptotic morphology of SGC-7901 cells was clear, exhibiting cell protuberance, concentrated cytoplasms and apoptotic bodies. Following 24 h of treatment, the MMP of the SGC-7901 cells decreased. In addition, after 48 h, the expression of cyt-c was shown to be upregulated, while the expression levels of pro-caspase-9 and pro-caspase-3 in the SGC-7901 cells were shown to be downregulated. In conclusion, apoptosis can be induced in SGC-7901 cells by podophyllotoxin, potentially via a mitochondrial pathway, indicating that podophyllotoxin may be a potent agent for cancer treatment.

Highlights

  • Gastric cancer (GC) is one of the most common cancers worldwide, in East Asia and East Europe

  • The inhibition of cell growth and apoptosis induced by podophyllotoxin was investigated in the human GC SGC‐7901 cell line, and the underlying mechanism was studied through the mitochondrial pathway

  • The MTT assay revealed that following treatment with various concentrations of podophyllotoxin for 72 h, podophyllotoxin exhibited an inhibitory effect on the proliferation of SGC‐7901 cells in a concentration‐dependent manner

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Summary

Introduction

Gastric cancer (GC) is one of the most common cancers worldwide, in East Asia and East Europe. Despite advances in surgery and chemotherapy for colon cancer, the outcomes of anticancer therapy remain unsatisfactory, further improvements are required. A number of pharmacological experiments have demonstrated that numerous naturally active components, isolated from plants and herbs, exhibit antitumor effects and may be potent agents for cancer treatment [2,3]. Podophyllotoxin is a lignan extracted from the Podophyllum plant, with a molecular formula of C22H22O8 and a molecular weight of 414 Da. Podophyllotoxin is a lignan extracted from the Podophyllum plant, with a molecular formula of C22H22O8 and a molecular weight of 414 Da This compound and its derivatives have great significance as antineoplastic drugs and antiviral agents due to the biological activities that they exhibit. Studies investigating the antitumor effect on GC are limited [9] and the molecular mechanism remains unclear. The inhibition of cell growth and apoptosis induced by podophyllotoxin was investigated in the human GC SGC‐7901 cell line, and the underlying mechanism was studied through the mitochondrial pathway

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