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Journal of Chinese Integrative Medicine ›› 2010, Vol. 8 ›› Issue (9): 870-876.doi: 10.3736/jcim20100911

• Original Experimental Research • Previous Articles     Next Articles

Tea polyphenol inhibits colorectal cancer with microsatellite instability by regulating the expressions of HES1, JAG1, MT2A and MAFA

YY Xu,HY Jin,XZ Tan,XF Liu,YJ Ding   

  1. National Center of Colorectal Surgery, The 3rd Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210001, Jiangsu Province, China
  • Received:2010-03-05 Accepted:2010-06-18 Online:2010-09-20 Published:2010-09-15

Objective

To investigate the mechanism of tea polyphenol in inhibiting microsatellite instability (MSI) of colorectal cancer.
Methods

Using LoVo cells and SW480 cells treated with aqueous solution of tea polyphenol, cell proliferation was detected by methyl thiazolyl tetrazolium (MTT) method, changes in microsatellite sequences were detected by genescan method and changes in gene expression of LoVo cells were detected by illumina expression arrays and quantitative real-time polymerase chain reaction (PCR).
Results

The proliferation inhibition rates of LoVo and SW480 cells treated with tea polyphenol increased with the increasing of drug concentration and showed an increasing tendency with time. The proliferation inhibition rate of LoVo cells with tea polyphenol was higher than that of SW480 cells, and there was a significant difference in the proliferation inhibition rates at 24 h, 72 h and one week. The microsatellite sequence of LoVo cells treated with tea polyphenol remained stable. The gene expression arrays and quantitative real-time PCR suggested that tea polyphenol inhibited the gene expressions of MT2A, MAFA, HES1 and JAG1 nearly two-fold over controls. It was also found that tea polyphenol inhibited the BAX and p38 genes with a more than two-fold difference but did not significantly inhibit the nuclear factor-κB pathway.
Conclusion

Tea polyphenol significantly inhibited the proliferation of MSI colorectal cancer cells and stably maintained the microsatellite state in MSI colorectal cancer. Tea polyphenol inhibited the gene expressions of HES1, JAG1, MT2A and MAFA, up-regulated the gene expression of BAX and down-regulated that of P38. Further research is required to investigate how these pathways are interrelated.

Key words: Tea polyphenols, Colorectal cancer, Microsatellite instability, Gene expression

Table 1

Forward and reverse primers used for real-time fluorescent quantitative PCR"

Figure 2

Inhibition rate on LoVo cells of tea polyphenol at different times"

Figure 2

Inhibition rate on SW480 cells of tea polyphenol at different times"

Table 2

Length of miscrosatellite marker after treatment with tea polyphenol"

Table 3

Up-regulated and down-regulated genes tested by expression microarray in LoVo cells after treatment with tea polyphenol"

Table 4

Expressions of mRNAs detected by real-time fluorescent quantitative PCR in LoVo cells"

[1] de La Chapelle A .Microsatellite instability phenotype of tumors: genotyping or immunohistochemistry? The jury is still out[J].J Clin Oncol, 2002, 20: 897-899
doi: 10.1200/JCO.2002.20.4.897
[2] Jin HY, Liu X, Li VK, Ding Y, Yang B, Geng J, Lai R, Ding S, Ni M, Zhao R .Detection of mismatch repair gene germline mutation carrier among Chinese population with colorectal cancer[J].BMC Cancer, 2008, 8: 44
doi: 10.1186/1471-2407-8-44
[3] Rüschoff J, Wallinger S, Dietmaier W, Bocker T, Brockhoff G, Hofstdter F, Fishel R .Aspirin suppresses the mutator phenotype associated with hereditary nonpolyposis colorectal cancer by genetic selection[J]. Proc Natl Acad Sci U S A, 1998,95(19):11301-11306
doi: 10.1073/pnas.95.19.11301
[4] Khan N, Afaq F, Saleem M, Ahmad N, Mukhtar H . Targeting multiple signaling pathways by green tea polyphenol(-)-epigallocatechin-3-gallate[J]. Cancer Res, 2006,66(5):2500-2505.
doi: 10.1158/0008-5472.CAN-05-3636
[5] Coyle CH, Philips BJ, Morrisroe SN, Chancellor MB, Yoshimura N . Antioxidant effects of green tea and its polyphenols on bladder cells[J]. Life Sci, 2008,83(1-2):12-18
doi: 10.1016/j.lfs.2008.04.010 pmid: 2490630
[6] Yang CS, Lambert JD, Sang S . Antioxidative and anti-carcinogenic activities of tea polyphenols[J]. Arch Toxicol, 2009,83(1):11-21
doi: 10.1007/s00204-008-0372-0 pmid: 19002670
[7] Lin Y, Kikuchi S, Tamakoshi A, Yagyu K, Obata Y, Kurosawa M, Inaba Y, Kawamura T, Motohashi Y, Ishibashi T; JACC Study Group . Green tea consumption and the risk of pancreatic cancer in Japanese adults[J]. Pancreas, 2008,37(1):25-30
doi: 10.1097/MPA.0b013e318160a5e2 pmid: 18580440
[8] Goel A, Chang DK, Ricciardiello L, Gasche C, Boland CR . A novel mechanism for aspirin-mediated growth inhibition of human colon cancer cells[J]. Clin Cancer Res, 2003,9(1):383-390
doi: 10.1159/000074533 pmid: 12538492
[9] Kumar N, Shibata D, Helm J, Coppola D, Malafa M .Green tea polyphenols in the prevention of colon cancer[J].Front Biosci, 2007, 12: 2309-2315
doi: 10.2741/2233 pmid: 17127241
[10] Thangapazham RL, Singh AK, Sharma A, Warren J, Gaddipati JP, Maheshwari RK . Green tea polyphenols and its constituent epigallocatechin gallate inhibit proliferation of human breast cancer cells in vitro and in vivo[J]. Cancer Lett, 2007,245(1-2):232-241
doi: 10.1016/j.canlet.2006.01.027
[11] Zhang CL, Hu JF, Qu JB, Yuan XY, Yu SF, Han HF . The study of antimutagenic value of Chinese herbs by Ames Test[J]. Wei Sheng Du Li Xue Za Zhi, 2002,16(1):66
doi: 10.3969/j.issn.1002-3127.2002.01.026
张春玲, 胡峻峰, 曲江斌, 袁晓燕, 于素芳, 韩惠芬 . Ames试验检测几种中草药及绿茶的抗诱变作用[J]. 卫生毒理学杂志, 2002,16(1):66
doi: 10.3969/j.issn.1002-3127.2002.01.026
[12] Sang L, Coller HA, Roberts JM . Control of the reversibility of cellular quiescence by the transcriptional repressor HES1[J]. Science, 2008,321(5892):1095-1100
doi: 10.1126/science.1155998
[13] Reedijk M, Odorcic S, Zhang H, Chetty R, Tennert C, Dickson BC, Lockwood G, Gallinger S, Egan SE . Activation of Notch signaling in human colon adenocarcinoma[J]. Int J Oncol, 2008,33(6):1223-1229
doi: 10.3892/ijo_00000112 pmid: 19020755
[14] Radtke F, Raj K . The role of NOTCH in tumorigenesis:oncogene or tumor suppressor?[J]. Nat Rev Cancer, 2003,3(10):756-767
doi: 10.1038/nrc1186 pmid: 14570040
[15] Puca R, Nardinocchi L, Bossi G, Sacchi A, Rechavi G, Givol D, D’Orazi G .Restoring wtp53 activity in HIPK2 depleted MCF7 cells by modulating metallothionein and zinc[J]. Exp Cell Res, 2009,315(1):67-75
doi: 10.1016/j.yexcr.2008.10.018
[16] Yang M, Chitambar CR . Role of oxidative stress in the induction of metallothionein-2A and heme oxygenase-1 gene expression by the antineoplastic agent gallium nitrate in human lymphoma cells[J]. Free Radic Biol Med, 2008,45(6):763-772
doi: 10.1016/j.freeradbiomed.2008.05.031
[17] Rocques N, Abou Zeid N, Sii-Felice K, Lecoin L, Felder-Schmittbuhl MP, Eychène A, Pouponnot C . GSK-3-mediated phosphorylation enhances Maf-transforming activity[J]. Mol Cell, 2007,28(4):584-597
doi: 10.1016/j.molcel.2007.11.009 pmid: 18042454
[18] Vanhoose AM, Samaras S, Artner I, Henderson E, Hang Y, Stein R . MafA and MafB regulate Pdx1 transcription through the Area II control region in pancreatic beta cells[J]. J Biol Chem, 2008,283(33):22612-22619
doi: 10.1074/jbc.M802902200
[19] Ahmad N, Feyes DK, Nieminen AL, Agarwal R, Mukhtar H . Green tea constituent epigallocatechin-3-gallate and induction of apoptosis and cell cycle arrest in human carcinoma cells[J]. J Natl Cancer Inst, 1997,89(24):1881-1886
doi: 10.1093/jnci/89.24.1881
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