Berberine inhibits the growth of human colorectal adenocarcinoma in vitro and in vivo
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ORIGINAL PAPER
Berberine inhibits the growth of human colorectal adenocarcinoma in vitro and in vivo Yuchen Cai • Qing Xia • Rongzhen Luo Peiyu Huang • Yueli Sun • Yanxia Shi • Wenqi Jiang
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Received: 28 November 2012 / Accepted: 18 March 2013 Ó The Japanese Society of Pharmacognosy and Springer Japan 2013
Abstract Berberine is an alkaloid isolated from the Chinese herbal medicine Huanglian, and has long been used as an antibiotic. Its antineoplastic properties were subsequently discovered in vitro. The purpose of this study was to investigate the effects of berberine on the growth of human colorectal carcinoma cells in vitro and in vivo. The results showed that berberine inhibited human colorectal adenocarcinoma (LoVo) cell growth in a time- and dose-dependent manner. A WST-1 assay showed that the IC50 value after 72 h was 40.79 ± 4.11 lM. Cell cycle analysis of 40 lM berberine-treated LoVo cells by flow cytometry showed accumulation of cells in the G2/M phase. The inhibition of LoVo cell growth by berberine was associated with the suppression of cyclin B1, cdc2, and cdc25c proteins. Berberine at a dose of 50 mg kg-1 day-1 showed inhibitory rates of 45.3 % in a human colorectal adenocarcinoma xenograft in nude mice. The combination of berberine and 5-fluorouracil (5-FU) had a higher inhibitory Y. Cai Q. Xia R. Luo P. Huang Y. Sun Y. Shi W. Jiang State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, People’s Republic of China Y. Cai Y. Sun Experimental Research Department, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, People’s Republic of China Q. Xia R. Luo P. Huang Y. Shi (&) W. Jiang (&) Department of Medical Oncology, Sun Yat-sen University Cancer Center, Sun Yat-sen University, 651 Dongfeng Road East, Guangzhou, Guangdong, People’s Republic of China e-mail: [email protected] W. Jiang e-mail: [email protected]
rate (59.8 %) than the berberine group (36.4 %, P = 0.01), but no significant difference was observed between the 5-FU group (43.0 %, P = 0.06) and the combination group. These results support the possibility that berberine may be useful as an alternative therapy for colorectal carcinoma. Keywords Berberine Colorectal carcinoma Cell cycle arrest In vivo
Introduction Berberine (BER)—2,3-methylenedioxy-9,10-dimethoxyprotoberberine chloride—is a benzyl tetra isoquinoline alkaloid extracted from plants of the genera Berberis and Coptis [1, 2]. Berberine has a marked spectrum of biological activities including anti-inflammatory [3, 4], antimicrobial [5], and antiviral [6] effects. It also possesses antitumor effects in a wide variety of human cancer cells including tongue squamous carcinoma [7], esophageal cancer [8], nasopharyngeal carcinoma [9], breast cancer [10], hepatoma [11], lung cancer [12, 13], and gastric carcinoma [14]. Recently, due to its low toxicity and low cost, the use of berberine has attracted great attention as an alternative anti-tumor therapy. Notably,
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