Antiproliferative and apoptotic effects of β-elemene on human hepatoma HepG2 cells

Zhi-Jun Dai,Wang-Feng Lu,Wei Tang,Xiao-Bin Ma,Wen-Ying Wu,Hua-Feng Kang,Jie Gao,Xi-Jing Wang,Wei-Li Min

doi:10.1186/1475-2867-13-27

Abstract

Backgroundβ-elemene, a natural sesquiterpene extracted from the essential oils of Curcuma aromatica Salisb, has been shown to be effective against a wide range of tumors. In this study, the antitumor effect of β-elemene on a human hepatoma cell line, HepG2, and the mechanism involved have been investigated.MethodsMTT assay was used to determine the growth inhibition of hepatoma HepG2 cells in vitro. Apoptosis of HepG2 cells were demonstrated by fluorescence microscope with Hoechst 33258 staining and flow cytometry with Annexin V-FITC/PI double staining. Flow cytometry was performed to analyze the cell cycle distribution of HepG2 cells. The mRNA and protein expression of Fas and FasL were measured by RT-PCR and Western blot analysis.ResultsMTT results showed that β-elemene could inhibit the proliferation of HepG2 cells in a time- and dose- dependent manner. Our results showed β-elemene had positive effect on apoptosis through fluorescence microscope and flow cytometry assay. Furthermore, β-elemene could induce the cell cycle arrest of the HepG2 cells in the G2/M phase. Fas and FasL expression were obviously increased after β-elemene treatment in both mRNA and protein level.ConclusionThe present study indicates that β-elemene can effectively inhibit proliferation and induce apoptosis in hepatoma HepG2 cells, and the apoptosis induction is related with up-regulating of Fas/FasL expression.

Highlights

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second leading cause of cancer-related deaths worldwide [1]
The aim of the present study is to investigate the antitumor effect of βelemene on human hepatoma HepG2 cells and the molecular mechanism involved
The percentage of cells in the β-elemene treated groups significantly decreased at the S phase and G0/G1 phase, simultaneous increased at the G2/M phase. These results suggest that β-elemene can induce cell cycle arrest at the G2/M phase in HepG2 cells (Figure 5)

Summary

Introduction

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second leading cause of cancer-related deaths worldwide [1]. The causes of HCC includes HBV or HCV infection, alcohol intake, smoking and aflatoxin. The treatment of patients with HCC is challenging because of the array of patient-specific (medical comorbidities), tumor-specific (size, number, location, and vascular involvement), and liver-specific (parenchymal reserve) variables that impact our ability to treat patients safely and effectively [3]. Sorafenib is the first molecular inhibitor to be approved by the FDA for the treatment of advanced HCC. Prior to the arrival of sorafenib, doxorubicin was routinely used as a single drug for advanced HCC, but has shown inefficacy, with a response rate of about 15-20%. Other chemotherapy agents, such as epirubicin, cisplatin, 5-fluorouracil and their combinations, demonstrate even lower efficacy [6]

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