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Effect of Carotenoids on the Growth of HT-29 Human Colon Cancer Cells

Carotenoids가 인체의 대장암 세포인 HT-29 세포의 증식에 미치는 영향

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  • Frederick Khachik (Joint Institute for Food Safety & Applied Nutrition, University of Maryland) ;
  • 김은지 (한림대학교 실버생물산업기술연구센터) ;
  • 정재인 (한림대학교 생명과학부) ;
  • 이현숙 (한림대학교 생명과학부) ;
  • 강일준 (한림대학교 생명과학부) ;
  • ;
  • 윤정한 (한림대학교 생명과학부)
  • Published : 2003.04.01

Abstract

Epidemiological studies have observed a negative association between increased consumption of green and yellow vegetables and cancer incidence. These vegetables contain carotenoids, which are reported to exhibit anticarcinogenic effects. Overexpression of ErbB2 and ErbB3 genes is a frequent event in several human cancers. The present study was performed to determine whether $\alpha$-carotene, $\beta$-carotene, lutein, or lycopene inhibits cell growth and to assess such an effect is related to changes in the levels of the ErbB receptor family and tile ErbB3 receptor signaling pathway in HT-29 cells. HT-29 cells were cultured in serum-free medium in the presence of various concentrations (0~100 $\mu$M) of the individual carotenoids. $\alpha$ -Carotene and lycopene significantly inhibited cell growth in a dose-dependent manner, whereas lutein slightly inhibited cell growth and $\beta$-carotene increased cell growth. Lycopene is more potent than $\alpha$ -carotene in inhibiting HT-29 cell growth. Lycopene inhibited DNA synthesis and induced apoptosis of HT-29 cells. The ErbB3 ligand heregulin (HRG) increased cell growth but did not prevent the lycopene-induced inhibition of cell growth. Lycopene decreased ErbB2 protein levels in a dose-dependent manner. Immunoprecipitation/Western blot studies revealed that lycopene inhibited HRG-induced phosphorylation of ErbB3, recruitment of the 985 regulatory subunit of phosphatidylinositol 3-kinase (PI3K) to the ErbB3 receptor, and phosphorylation of Akt. These results indicate that downregulation of ErbB2/ErbB3/PI3K/Akt signaling may be one of the mechanisms by which lycopene inhibits HT-29 cell pro-liferation and induces apoptosis.

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