The study of effect of tea polyphenols on microsatellite instability colorectal cancer and its molecular mechanism.
BACKGROUND
Tea polyphenol has been shown to have anti-colorectal cancer and anti-gene mutation effects, although the mechanism of inhibition of microsatellite instability (MSI) colorectal cancer is not known.


METHODS
Using LoVo, HCT-116, HT-29, and SW480 cells treated with an aqueous solution of tea polyphenol, cell proliferation was detected by the methyl thiazolyl tetrazolium method, changes in microsatellite sequences by the Genescan method and changes in the gene expression of LoVo cells using Illumina expression arrays.


RESULTS
The proliferation inhibition rate of LoVo, HCT-116, HT-29, and SW480 cells treated with tea polyphenol increased with increasing drug concentration and showed an increasing tendency with time. The proliferation inhibition rate of LoVo and HCT-116 cells with tea polyphenols was higher than that of HT-29 and SW480 cells, and there was a significant difference in the proliferation inhibition rate at 24, 72 h and 1 week. The microsatellite sequence of LoVo cells treated with tea polyphenols remained stable.


CONCLUSIONS
The gene expression arrays and quantitative RT-PCR suggested that tea polyphenol inhibited the gene expression of metallothionein 2A (MT2A), transcription factor (MAFA), hairy and enhancer of split 1 (HES1), and jagged1 (JAG1) nearly twofold over controls. It was also found that tea polyphenol inhibited the BAX and p38 genes with a more than twofold difference but did not significantly inhibited the NFκB pathway.


CONCLUSIONS
Tea polyphenol significantly inhibited the proliferation of MSI colorectal cancer signals maintained stable at the microsatellite state in MSI colorectal cancer. Tea polyphenol inhibited the gene expression of HES1, JAG1, MT2A, and MAFA but upregulated the gene expression of BAX and downregulated that of (P)38. Further research is required to investigate how these pathways are interrelated.
Jin
Heiying
H
National Center of Colorectal Surgery, The 3rd affiliated Hospital of Nanjing University of Traditional Chinese Medicine, 1 Jinling Road, Jiangsu, 210001, China. jinheiying@yahoo.com.cn
Tan
Xuanzhong
X
Liu
Xiufang
X
Ding
Yijiang
Y
D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D002135:Calcium-Binding Proteins / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D000072100:Jagged-1 Protein; D051473:Maf Transcription Factors, Large / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D008668:Metallothionein / Q000235:genetics; D053842:Microsatellite Instability / Q000187:drug effects*; D010636:Phenols / Q000494:pharmacology*; D059808:Polyphenols; D000072099:Serrate-Jagged Proteins; D013662:Tea / Q000737:chemistry; D000072056:Transcription Factor HES-1; D051028:bcl-2-Associated X Protein / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics
D051792:Basic Helix-Loop-Helix Proteins; D002135:Calcium-Binding Proteins; D005419:Flavonoids; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D051473:Maf Transcription Factors, Large; D008565:Membrane Proteins; D008668:Metallothionein; D010636:Phenols; D059808:Polyphenols; D000072099:Serrate-Jagged Proteins; D013662:Tea; D000072056:Transcription Factor HES-1; D051028:bcl-2-Associated X Protein; D048051:p38 Mitogen-Activated Protein Kinases; C000606273:JAG1 protein, human; C485159:MAFA protein, human; C491053:MT2A protein, human; C078493:HES1 protein, human