Molecular mechanisms of apoptosis induced by magnolol in colon and liver cancer cells

Shyr Yi Lin, Yu Tza Chang, Jean-Dean Liu, Chung Hsun Yu, Yuan Soon Ho, Yi-Hsuan Lee, Wen Sen Lee

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

Magnolol has been reported to have anticancer activity. In this study we found that treatment with 100 μm magnolol induced apoptosis in cultured human hepatoma (Hep G2) and colon cancer (COLO 205) cell lines but not in human untransformed gingival fibroblasts and human umbilical vein endothelial cells. Our investigation of apoptosis in Hep G2 cells showed a sequence of associated intracellular events that included (a) increased cytosolic free Ca2+; (b) increased translocation of cytochrome c (Cyto c) from mitochondria to cytosol; (c) activation of caspase 3, caspase 8, and caspase 9; and (d) downregulation of bcl-2 protein. Pretreatment of the cells with the phospholipase C inhibitor 1-[6-[[(17β)-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1 H-pyrrole-2,5-dione (U73122) or the intracellular chelator of Ca2+ 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid acetoxymethyl ester (BAPTA/AM) inhibited the subsequent magnolol augmentation of [ca2+]i and also the activation of caspase-8 and caspase-9, so that the occurrence of apoptosis in those cells was greatly reduced. Pretreatment of the cells with ZB4 (which disrupts the Fas response mechanism) also decreased the subsequent magnolol-induced caspase-8 activation and reduced the occurrence of apoptosis. We interpreted these findings to indicate that the above-listed sequence of intracellular events led to the apoptosis seen in Hep G2 cells and that [Ca2+]i, Cyto c, and Fas function as intracellular signals to coordinate those events.

Original languageEnglish
Pages (from-to)73-83
Number of pages11
JournalMolecular Carcinogenesis
Volume32
Issue number2
DOIs
Publication statusPublished - 2001

Fingerprint

Liver Neoplasms
Colonic Neoplasms
Caspase 8
Apoptosis
Caspase 9
Hep G2 Cells
Cytochromes c
Trientine
Pyrroles
Ethane
Human Umbilical Vein Endothelial Cells
Type C Phospholipases
Chelating Agents
Caspase 3
Cytosol
Hepatocellular Carcinoma
Mitochondria
Esters
Down-Regulation
Fibroblasts

Keywords

  • Bcl-2
  • Calcium
  • Caspases
  • Cytochrome c
  • Fas

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology

Cite this

Molecular mechanisms of apoptosis induced by magnolol in colon and liver cancer cells. / Lin, Shyr Yi; Chang, Yu Tza; Liu, Jean-Dean; Yu, Chung Hsun; Ho, Yuan Soon; Lee, Yi-Hsuan; Lee, Wen Sen.

In: Molecular Carcinogenesis, Vol. 32, No. 2, 2001, p. 73-83.

Research output: Contribution to journalArticle

@article{13be245cc2634296a37e8ed68d550756,
title = "Molecular mechanisms of apoptosis induced by magnolol in colon and liver cancer cells",
abstract = "Magnolol has been reported to have anticancer activity. In this study we found that treatment with 100 μm magnolol induced apoptosis in cultured human hepatoma (Hep G2) and colon cancer (COLO 205) cell lines but not in human untransformed gingival fibroblasts and human umbilical vein endothelial cells. Our investigation of apoptosis in Hep G2 cells showed a sequence of associated intracellular events that included (a) increased cytosolic free Ca2+; (b) increased translocation of cytochrome c (Cyto c) from mitochondria to cytosol; (c) activation of caspase 3, caspase 8, and caspase 9; and (d) downregulation of bcl-2 protein. Pretreatment of the cells with the phospholipase C inhibitor 1-[6-[[(17β)-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1 H-pyrrole-2,5-dione (U73122) or the intracellular chelator of Ca2+ 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid acetoxymethyl ester (BAPTA/AM) inhibited the subsequent magnolol augmentation of [ca2+]i and also the activation of caspase-8 and caspase-9, so that the occurrence of apoptosis in those cells was greatly reduced. Pretreatment of the cells with ZB4 (which disrupts the Fas response mechanism) also decreased the subsequent magnolol-induced caspase-8 activation and reduced the occurrence of apoptosis. We interpreted these findings to indicate that the above-listed sequence of intracellular events led to the apoptosis seen in Hep G2 cells and that [Ca2+]i, Cyto c, and Fas function as intracellular signals to coordinate those events.",
keywords = "Bcl-2, Calcium, Caspases, Cytochrome c, Fas",
author = "Lin, {Shyr Yi} and Chang, {Yu Tza} and Jean-Dean Liu and Yu, {Chung Hsun} and Ho, {Yuan Soon} and Yi-Hsuan Lee and Lee, {Wen Sen}",
year = "2001",
doi = "10.1002/mc.1066",
language = "English",
volume = "32",
pages = "73--83",
journal = "Molecular Carcinogenesis",
issn = "0899-1987",
publisher = "Wiley-Liss Inc.",
number = "2",

}

TY - JOUR

T1 - Molecular mechanisms of apoptosis induced by magnolol in colon and liver cancer cells

AU - Lin, Shyr Yi

AU - Chang, Yu Tza

AU - Liu, Jean-Dean

AU - Yu, Chung Hsun

AU - Ho, Yuan Soon

AU - Lee, Yi-Hsuan

AU - Lee, Wen Sen

PY - 2001

Y1 - 2001

N2 - Magnolol has been reported to have anticancer activity. In this study we found that treatment with 100 μm magnolol induced apoptosis in cultured human hepatoma (Hep G2) and colon cancer (COLO 205) cell lines but not in human untransformed gingival fibroblasts and human umbilical vein endothelial cells. Our investigation of apoptosis in Hep G2 cells showed a sequence of associated intracellular events that included (a) increased cytosolic free Ca2+; (b) increased translocation of cytochrome c (Cyto c) from mitochondria to cytosol; (c) activation of caspase 3, caspase 8, and caspase 9; and (d) downregulation of bcl-2 protein. Pretreatment of the cells with the phospholipase C inhibitor 1-[6-[[(17β)-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1 H-pyrrole-2,5-dione (U73122) or the intracellular chelator of Ca2+ 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid acetoxymethyl ester (BAPTA/AM) inhibited the subsequent magnolol augmentation of [ca2+]i and also the activation of caspase-8 and caspase-9, so that the occurrence of apoptosis in those cells was greatly reduced. Pretreatment of the cells with ZB4 (which disrupts the Fas response mechanism) also decreased the subsequent magnolol-induced caspase-8 activation and reduced the occurrence of apoptosis. We interpreted these findings to indicate that the above-listed sequence of intracellular events led to the apoptosis seen in Hep G2 cells and that [Ca2+]i, Cyto c, and Fas function as intracellular signals to coordinate those events.

AB - Magnolol has been reported to have anticancer activity. In this study we found that treatment with 100 μm magnolol induced apoptosis in cultured human hepatoma (Hep G2) and colon cancer (COLO 205) cell lines but not in human untransformed gingival fibroblasts and human umbilical vein endothelial cells. Our investigation of apoptosis in Hep G2 cells showed a sequence of associated intracellular events that included (a) increased cytosolic free Ca2+; (b) increased translocation of cytochrome c (Cyto c) from mitochondria to cytosol; (c) activation of caspase 3, caspase 8, and caspase 9; and (d) downregulation of bcl-2 protein. Pretreatment of the cells with the phospholipase C inhibitor 1-[6-[[(17β)-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1 H-pyrrole-2,5-dione (U73122) or the intracellular chelator of Ca2+ 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid acetoxymethyl ester (BAPTA/AM) inhibited the subsequent magnolol augmentation of [ca2+]i and also the activation of caspase-8 and caspase-9, so that the occurrence of apoptosis in those cells was greatly reduced. Pretreatment of the cells with ZB4 (which disrupts the Fas response mechanism) also decreased the subsequent magnolol-induced caspase-8 activation and reduced the occurrence of apoptosis. We interpreted these findings to indicate that the above-listed sequence of intracellular events led to the apoptosis seen in Hep G2 cells and that [Ca2+]i, Cyto c, and Fas function as intracellular signals to coordinate those events.

KW - Bcl-2

KW - Calcium

KW - Caspases

KW - Cytochrome c

KW - Fas

UR - http://www.scopus.com/inward/record.url?scp=0035168066&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035168066&partnerID=8YFLogxK

U2 - 10.1002/mc.1066

DO - 10.1002/mc.1066

M3 - Article

C2 - 11746819

AN - SCOPUS:0035168066

VL - 32

SP - 73

EP - 83

JO - Molecular Carcinogenesis

JF - Molecular Carcinogenesis

SN - 0899-1987

IS - 2

ER -