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Indole-3-carbinol induces apoptosis through p53 and activation of caspase-8 pathway in lung cancer A549 cells

Indole-3-carbinol (I3C) has anti-tumor effects in various cancer cell lines. However, the anti-tumor effect of I3C on human lung cancers has been rarely reported. We investigated the anti-tumor effects and its mechanism of I3C on human lung carcinoma A549 cell line. Treatment of the A549 cells with...

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Published in:Food and chemical toxicology 2010-03, Vol.48 (3), p.883-890
Main Authors: Choi, Hee-Sook, Cho, Min-Chul, Lee, Hee Gu, Yoon, Do-Young
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description Indole-3-carbinol (I3C) has anti-tumor effects in various cancer cell lines. However, the anti-tumor effect of I3C on human lung cancers has been rarely reported. We investigated the anti-tumor effects and its mechanism of I3C on human lung carcinoma A549 cell line. Treatment of the A549 cells with I3C significantly reduced cell proliferation, increased formations of fragmented DNA and apoptotic body, and induced cell cycle arrest at G0/G1 phase. I3C increased not only the protein levels of cyclin D1, phosphorylated p53, and p21 but also the expression of Fas mRNA. Cleavage of caspase-9, -8, -3 and PARP also was increased by I3C. Treatment with wortmannin significantly suppressed both I3C-induced Ser15 phosphorylation and accumulation of p53 protein. The inhibition of caspase-8 by z-IETD-FMK significantly decreased cleavage of procaspase-8,-3 and PARP in I3C-treated A549 cells. Taken together, these results demonstrate that I3C induces cell cycle arrest at G0/G1 through the activation of p-p53 at Ser 15 and induces caspase-8 mediated apoptosis via the Fas death receptor. This molecular mechanism for apoptotic effect of I3C on A549 lung carcinoma cells may be a first report and suggest that I3C may be a preventive and therapeutic agent against lung cancer.
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However, the anti-tumor effect of I3C on human lung cancers has been rarely reported. We investigated the anti-tumor effects and its mechanism of I3C on human lung carcinoma A549 cell line. Treatment of the A549 cells with I3C significantly reduced cell proliferation, increased formations of fragmented DNA and apoptotic body, and induced cell cycle arrest at G0/G1 phase. I3C increased not only the protein levels of cyclin D1, phosphorylated p53, and p21 but also the expression of Fas mRNA. Cleavage of caspase-9, -8, -3 and PARP also was increased by I3C. Treatment with wortmannin significantly suppressed both I3C-induced Ser15 phosphorylation and accumulation of p53 protein. The inhibition of caspase-8 by z-IETD-FMK significantly decreased cleavage of procaspase-8,-3 and PARP in I3C-treated A549 cells. 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identifier ISSN: 0278-6915
ispartof Food and chemical toxicology, 2010-03, Vol.48 (3), p.883-890
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source ScienceDirect Freedom Collection
subjects A549
anticarcinogenic activity
Anticarcinogenic Agents - toxicity
Apoptosis
Apoptosis - drug effects
biochemical pathways
Biological and medical sciences
Blotting, Western
Caspase 8 - drug effects
caspase-8 pathway
cell culture
Cell Cycle - drug effects
Cell cycle arrest
Cell Line, Tumor
Cell Proliferation - drug effects
Cyclin D1 - biosynthesis
cytotoxicity
DNA Repair - drug effects
Enzyme Activation - drug effects
Fas Ligand Protein - physiology
Flow Cytometry
Genes, p53 - drug effects
human cell lines
Humans
Indicators and Reagents
Indole-3-carbinol
indoles
Indoles - toxicity
Lung cancer
lung neoplasms
Lung Neoplasms - pathology
Medical sciences
Phosphorylation
Pneumology
proteins
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction - drug effects
Toxicology
Tumors of the respiratory system and mediastinum
title Indole-3-carbinol induces apoptosis through p53 and activation of caspase-8 pathway in lung cancer A549 cells
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