|
KMID : 0893420220230050074
|
|
Journal of Veterinary Science
2022 Volume.23 No. 5 p.74 ~ p.74
|
|
|
Epigallocatechin-3-gallate suppresses hemin-aggravated colon carcinogenesis through Nrf2-inhibited mitochondrial reactive oxygen species accumulation
|
|
Seok Ju-Hyung
Kim Dae-Hyun
Kim Hye-Jih
Jo Hang-Hyo
Kim Eun-Young
Jeong Jae-Hwang
Park Young-Seok
Lee Sang-Hun
Kim Dae-Joong
Nam Sang-Yoon
Lee Beom-Jun
Lee Hyun-Jik
|
|
|
Abstract
|
|
|
Background : Previous studies have presented evidence to support the significant association between red meat intake and colon cancer, suggesting that heme iron plays a key role in colon carcinogenesis. Epigallocatechin-3-gallate (EGCG), the major constituent of green tea, exhibits anti-oxidative and anti-cancer effects. However, the effect of EGCG on red meat-associated colon carcinogenesis is not well understood.
Objectives : We aimed to investigate the regulatory effects of hemin and EGCG on colon carcinogenesis and the underlying mechanism of action.
Methods : Hemin and EGCG were treated in Caco2 cells to perform the water-soluble tetrazolium salt-1 assay, lactate dehydrogenase release assay, reactive oxygen species (ROS) detection assay, real-time quantitative polymerase chain reaction and western blot. We investigated the regulatory effects of hemin and EGCG on an azoxymethane (AOM) and dextran sodium sulfate (DSS)-induced colon carcinogenesis mouse model.
Results : In Caco2 cells, hemin increased cell proliferation and the expression of cell cycle regulatory proteins, and ROS levels. EGCG suppressed hemin-induced cell proliferation and cell cycle regulatory protein expression as well as mitochondrial ROS accumulation. Hemin increased nuclear factor erythroid-2-related factor 2 (Nrf2) expression, but decreased Keap1 expression. EGCG enhanced hemin-induced Nrf2 and antioxidant gene expression. Nrf2 inhibitor reversed EGCG reduced cell proliferation and cell cycle regulatory protein expression. In AOM/DSS mice, hemin treatment induced hyperplastic changes in colon tissues, inhibited by EGCG supplementation. EGCG reduced the hemin-induced numbers of total aberrant crypts and malondialdehyde concentration in the AOM/DSS model.
Conclusions : We demonstrated that EGCG reduced hemin-induced proliferation and colon carcinogenesis through Nrf2-inhibited mitochondrial ROS accumulation.
|
|
|
KEYWORD
|
|
|
Hemin, colon cancer, epigallocatechin-3-gallate, reactive oxygen species, oxidative stress, nuclear respiratory factor 2
|
|
|
FullTexts / Linksout information
|
|
 
|
|
|
Listed journal information
|
|
|
|
|