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Effect of Lycopene on the Insulin-like Growth Factor-I Receptor Signaling Pathway in Human Colon Cancer HT-29 Cells

인간의 대장암 HT-29 세포주에서 라이코펜이 Insulin-like Growth Factor-I Receptor Signaling Pathway에 미치는 영향

  • ;
  • ;
  • ;
  • Frederick Khachik (Dept. of Chemistry & Biochemistry, Joint Institute for Food Safety & Applied Nutrition, University of Maryland) ;
  • 이현숙 (한림대학교 생명과학부 식품영양전공) ;
  • 정재인 (한림대학교 생명과학부 식품영양전공) ;
  • 강영희 (한림대학교 생명과학부 식품영양전공) ;
  • ;
  • 윤정한 (한림대학교 생명과학부 식품영양전공)
  • Published : 2003.04.01

Abstract

Epidemiological data suggest that lycopene has anticancer activities in humans. Insulin-like growth factor-I receptor (IGF-IR) is a transmembrane tyrosine kinase that mediates the biological actions of IGFs and may play an active role in cancer progression. Because our previous in vitro studies have indicated lycopene inhibits HT-29 cell growth, the aim of this study was to determine whether lycopene induces apoptotic cell death and the inhibitory effect of lycopene on HT-29 cell growth is related to changes in IGF-IR levels and the receptor's intracellular signalling pathways. HT-29 cells were incubated for 4 days in serum-free medium in the presence of 0, 25, 50, or 100 $\mu$M lycopene, and the DNA fragmentation assay was performed. Cells treated with lycopene produced a distinct oligonucleosomal ladder with different sizes of DNA fragments, a typical characteristic of cells undergoing apoptosis. HT-29 cells were cultured for 4 days in serum-free medium in the presence of 0~100 $\mu$M lycopene and IGF-I (10nM) was added for 0~60 minutes immediately prior to lysate preparations. Western blot analysis of total lysates revealed that lycopene decreased the levels of IRS-1, Akt, phosphatidylinositol 3-kinase (PI3K), and IGF-IR $\beta$-subunit, and increased the levels of the IGF-IR precursor dose dependently. Lycopene also decreased IGF-I-induced phosphorylation of IGF-IR$\beta$, IRS-1 and Akt, which were, at least in part, due to decreased expression of these proteins. These results suggest that lycopene induces apoptosis of HT-29 cells by inhibiting IGF-IR signaling thereby interfering with an IGF-II-driven autocrine growth loop, which is known to exist in this cell line.

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