Gleditsia sinensis thorn extract inhibits human colon cancer cells: the role of ERK1/2, G2/M‐phase cell cycle arrest and p53 expression

• Published in: Phytotherapy research 2010-12, Vol.24 (12), p.1870-1876
• Main Authors: Lee, Se‐Jung, Park, Keerang, Ha, Sang‐Do, Kim, Wun‐Jae, Moon, Sung‐Kwon
• Format: Article
• Language: English
• Subjects: Animals; Antitumor activity; Antitumor agents; Biological and medical sciences; Body weight; c-Jun amino-terminal kinase; Cdc2 protein; Cell cycle; Cell Cycle - drug effects; Cell Cycle Proteins - metabolism; cell growth; Cell Line, Tumor; Cell Proliferation - drug effects; Colon cancer; Colonic Neoplasms - drug therapy; Down-Regulation; Drugs, Chinese Herbal - pharmacology; ERK; Extracellular signal-regulated kinase; Extracellular Signal-Regulated MAP Kinases - metabolism; Flavonoids - pharmacology; G2/M-phase cell cycle arrest; Gene Expression Regulation, Neoplastic; General pharmacology; Gleditsia; Gleditsia - chemistry; Herbal medicines; Humans; JNK Mitogen-Activated Protein Kinases - metabolism; Malignancy; MAP kinase; Medical sciences; Mice; Mice, Nude; Molecular modelling; p38 Mitogen-Activated Protein Kinases - metabolism; p53; p53 protein; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Phosphorylation; Phytotherapy; Plant Extracts - pharmacology; Side effects; Tumor cells; Tumor Suppressor Protein p53 - metabolism; water extract of Gleditsia sinensis thorns; Xenograft Model Antitumor Assays; Xenografts
• ISSN: 0951-418X; 1099-1573; 1099-1573
• DOI: 10.1002/ptr.3214

The thorns of Gleditsia sinensis are used as a medicinal herb in China and Korea. However, the mechanisms responsible for the antitumor effects of the water extract of Gleditsia sinensis thorns (WEGS) remain unknown. HCT116 cells treated with the WEGS at a dose of 800 μg/mL (IC₅₀) showed a significant decrease in cell growth and an increase in cell cycle arrest during the G2/M‐phase. G2/M‐phase arrest was correlated with increased p53 levels and down‐regulation of the check‐point proteins, cyclinB1, Cdc2 and Cdc25c. In addition, treatment with WEGS induced phosphorylation of extracellular signal‐regulated kinase (ERK), p38 MAP kinase and JNK (c‐Jun N‐terminal kinases). Moreover, inhibition of ERK by treatment of cells with the ERK‐specific inhibitor PD98059 blocked WEGS‐mediated p53 expression. Similarly, blockage of ERK function in the WEGS‐treated cells reversed cell‐growth inhibition and decreased cell cycle proteins. Finally, in vivo WEGS treatment significantly inhibited the growth of HCT116 tumor cell xenografts in nude mice with no negative side effects, including loss of body weight. These results describe the molecular mechanisms whereby the WEGS might inhibit proliferation of colon cancer both in vitro and in vivo, suggesting that WEGS has potential as an anticancer agent for the treatment of malignancies. Copyright © 2010 John Wiley & Sons, Ltd.