Gleditsia sinensis thorn extract inhibits human colon cancer cells: the role of ERK1/2, G2/M-phase cell cycle arrest and p53 expression.
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.
Lee
Se-Jung
SJ
Department of Biotechnology, Chungju National University, Chungju, Chungbuk 380-702, South Korea; Department of Food Science and Technology, Chung-Ang University, Ansung 72-1, Korea.
Park
Keerang
K
Ha
Sang-Do
SD
Kim
Wun-Jae
WJ
Moon
Sung-Kwon
SK
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects*; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy*; D015536:Down-Regulation; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D031501:Gleditsia / Q000737:chemistry*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D010936:Plant Extracts / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D018797:Cell Cycle Proteins; D004365:Drugs, Chinese Herbal; D005419:Flavonoids; D010936:Plant Extracts; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one