Abstract Title:

Genistein synergizes with arsenic trioxide to suppress human hepatocellular carcinoma.

Abstract Source:

Cancer Sci. 2010 Apr ;101(4):975-83. Epub 2009 Dec 9. PMID: 20219070

Abstract Author(s):

Hongchi Jiang, Yong Ma, Xiaoning Chen, Shangha Pan, Bei Sun, Geoffrey W Krissansen, Xueying Sun

Article Affiliation:

Department of General Surgery, The Hepatosplenic Surgery Center, The First Affiliated Hospital of Harbin Medical University, Harbin, China. jianghc@vip.163.com


Arsenic trioxide (ATO) is of limited therapeutic benefit for the treatment of solid tumors. Genistein exhibits anticancer and pro-oxidant activities, making it a potential candidate to enhance the efficacy of ATO whose cytotoxicity is oxidation-sensitive. This study sought to determine whether genistein synergizes with ATO to combat hepatocellular carcinoma (HCC). Three human HCC cell lines, namely HepG2, Hep3B, and SK-Hep-1, were incubated with ATO, genistein, or ATO + genistein. The cells were also pretreated with antioxidant agents N-acetyl-L-cysteine (NAC) or butylated hydroxyanisole (BHA). Cell viability, apoptosis, intracellular reactive oxygen species (ROS), mitochondrial membrane potential (DeltaPsim), expression of Bcl-2, Bax, caspase-9, and -3, and release of cytochrome c into the cytosol were examined. The synergistic effect of ATO and genistein was also assessed using HepG2 xenografts subcutaneously established in BALB/c nude mice. The results show that genistein synergized with ATO to reduce viability, induce apoptosis, and diminish the DeltaPsim of cells. The combination therapy down-regulated Bcl-2 expression, up-regulated Bax expression, enhanced the activation of caspase-9 and -3, and increased the release of cytochrome c. The synergistic effect of ATO and genistein was diminished by pretreatment with NAC or BHA. Genistein increased the production of intracellular ROS, while ATO had little effect. Genistein synergized with a low dose of ATO (2.5 mg/kg) to significantly inhibit the growth of HepG2 tumors, and suppress cell proliferation and induce apoptosis in situ. There were no obvious side effects, as seen with a high dose of ATO (5 mg/kg). Combining genistein with ATO warrants investigation as a therapeutic strategy to combat HCC.

Study Type : In Vitro Study

Print Options

Key Research Topics

Sayer Ji
Founder of GreenMedInfo.com

Subscribe to our informative Newsletter & get Nature's Evidence-Based Pharmacy

Our newsletter serves 500,000 with essential news, research & healthy tips, daily.

Download Now

500+ pages of Natural Medicine Alternatives and Information.

This website is for information purposes only. By providing the information contained herein we are not diagnosing, treating, curing, mitigating, or preventing any type of disease or medical condition. Before beginning any type of natural, integrative or conventional treatment regimen, it is advisable to seek the advice of a licensed healthcare professional.

© Copyright 2008-2022 GreenMedInfo.com, Journal Articles copyright of original owners, MeSH copyright NLM.