Inhibition of epigallocatechin gallate on orthotopic colon cancer by upregulating the Nrf2-UGT1A signal pathway in nude mice.
Epigallocatechin gallate (EGCG), a key active ingredient in green tea, has many anti-carcinogenic activities. The aim of the present study was to investigate whether EGCG could prevent the occurrence or metastases of orthotopic colon cancer and probe the underlined mechanisms. We observed the inhibition of EGCG on growth and metastases of colon tumor implanted orthotopically in the cecum of nude mice. Immunohistochemistry and Western-blotting analysis were used to detect NF-E2-related factor 2 (Nrf2) protein expressions. RT-PCR was also applied to detect the mRNA levels of Nrf2, uridine 5'-diphosphate-glucuronosyltransferase (UGT) 1A, UGT1A8 and UGT1A10 in colon tumors. As a result, the inhibition rates on tumor growth in the 3 EGCG groups were significantly different (all p < 0.001) compared with the control group. In addition, different doses of EGCG were able to inhibit liver and pulmonary metastases to varying degrees. The protein level of Nrf2 and the mRNA levels of Nrf2, UGT1A, UGT1A8 and UGT1A10 significantly increased in EGCG-treated mice in comparison with the control group (all p < 0.01). The results demonstrated that EGCG has a preventive effect on the growth and liver and pulmonary metastases of orthotopic colon cancer in nude mice, and this anticancer effect could be partly caused by activating the Nrf2-UGT1A signal pathway.
Yuan
Jun-Hua
JH
Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, PR China.
Li
Yan-Qing
YQ
Yang
Xiao-Yun
XY
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000502:physiology*; D019073:HT29 Cells; D006801:Humans; D008175:Lung Neoplasms / Q000556:secondary; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D051267:NF-E2-Related Factor 2 / Q000032:analysis / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D015398:Signal Transduction / Q000187:drug effects*
D016588:Anticarcinogenic Agents; D051267:NF-E2-Related Factor 2; D012333:RNA, Messenger; D002392:Catechin; C045651:epigallocatechin gallate; D014453:Glucuronosyltransferase