ATM/ATR and SMAD3 pathways contribute to 3-indole-induced G1 arrest in cancer cells and xenograft models

Sin Ming Huang, Kwok Tung Lu, Yi-Ching Wang

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Background: 3-Indole inhibits lung cancer growth by apoptosis. Here, the growth inhibition mechanism besides apoptosis was further characterized. Materials and Methods: The Comet assay was used to examine 3-indole-induced DNA damage. Cell cycle distribution and protein expression were analyzed using flow cytometry, Western blotting and immunohistochemistry in cell and animal models. Results: 3-Indole induced dose-dependent DNA damage, which was reversed by reactive oxygen species (ROS) inhibitor in lung cancer cells. Cell cycle G 1 arrest was observed in the 3-indole-treated cells. DNA damage-responsive proteins involved in the ataxia telangiectasia mutated/ataxia telangiectasia and Rad3-related (ATM/ATR) pathway and G1 regulation proteins such as p21 and SMA- and MAD-related protein 3 (SMAD3) were induced in the cell models. The altered expression of ATM, ATR, checkpoint kinase 2 (CHK2), and cell division cycle 25 homolog A (CDC25A) were confirmed in xenograft models. Importantly, the 3-indole-induced ATM/ATR and transforming growth factor (TGF)-β/SMAD pathways were attenuated by ROS inhibitor. Conclusion: 3-Indole causes DNA damage and triggers ATM/ATR and SMAD3 signaling pathways to arrest lung cancer cells at the G1-phase.

Original languageEnglish
Pages (from-to)203-208
Number of pages6
JournalAnticancer Research
Volume31
Issue number1
Publication statusPublished - 2011 Jan

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Ataxia Telangiectasia
Heterografts
DNA Damage
Lung Neoplasms
Neoplasms
Proteins
Reactive Oxygen Species
Checkpoint Kinase 2
Cell Cycle
Apoptosis
Cell Cycle Proteins
Comet Assay
G1 Phase
Transforming Growth Factors
Growth
indole
mycophenolic adenine dinucleotide
Flow Cytometry
Animal Models
Western Blotting

All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Oncology

Cite this

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title = "ATM/ATR and SMAD3 pathways contribute to 3-indole-induced G1 arrest in cancer cells and xenograft models",
abstract = "Background: 3-Indole inhibits lung cancer growth by apoptosis. Here, the growth inhibition mechanism besides apoptosis was further characterized. Materials and Methods: The Comet assay was used to examine 3-indole-induced DNA damage. Cell cycle distribution and protein expression were analyzed using flow cytometry, Western blotting and immunohistochemistry in cell and animal models. Results: 3-Indole induced dose-dependent DNA damage, which was reversed by reactive oxygen species (ROS) inhibitor in lung cancer cells. Cell cycle G 1 arrest was observed in the 3-indole-treated cells. DNA damage-responsive proteins involved in the ataxia telangiectasia mutated/ataxia telangiectasia and Rad3-related (ATM/ATR) pathway and G1 regulation proteins such as p21 and SMA- and MAD-related protein 3 (SMAD3) were induced in the cell models. The altered expression of ATM, ATR, checkpoint kinase 2 (CHK2), and cell division cycle 25 homolog A (CDC25A) were confirmed in xenograft models. Importantly, the 3-indole-induced ATM/ATR and transforming growth factor (TGF)-β/SMAD pathways were attenuated by ROS inhibitor. Conclusion: 3-Indole causes DNA damage and triggers ATM/ATR and SMAD3 signaling pathways to arrest lung cancer cells at the G1-phase.",
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ATM/ATR and SMAD3 pathways contribute to 3-indole-induced G1 arrest in cancer cells and xenograft models. / Huang, Sin Ming; Lu, Kwok Tung; Wang, Yi-Ching.

In: Anticancer Research, Vol. 31, No. 1, 01.2011, p. 203-208.

Research output: Contribution to journalArticle

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N2 - Background: 3-Indole inhibits lung cancer growth by apoptosis. Here, the growth inhibition mechanism besides apoptosis was further characterized. Materials and Methods: The Comet assay was used to examine 3-indole-induced DNA damage. Cell cycle distribution and protein expression were analyzed using flow cytometry, Western blotting and immunohistochemistry in cell and animal models. Results: 3-Indole induced dose-dependent DNA damage, which was reversed by reactive oxygen species (ROS) inhibitor in lung cancer cells. Cell cycle G 1 arrest was observed in the 3-indole-treated cells. DNA damage-responsive proteins involved in the ataxia telangiectasia mutated/ataxia telangiectasia and Rad3-related (ATM/ATR) pathway and G1 regulation proteins such as p21 and SMA- and MAD-related protein 3 (SMAD3) were induced in the cell models. The altered expression of ATM, ATR, checkpoint kinase 2 (CHK2), and cell division cycle 25 homolog A (CDC25A) were confirmed in xenograft models. Importantly, the 3-indole-induced ATM/ATR and transforming growth factor (TGF)-β/SMAD pathways were attenuated by ROS inhibitor. Conclusion: 3-Indole causes DNA damage and triggers ATM/ATR and SMAD3 signaling pathways to arrest lung cancer cells at the G1-phase.

AB - Background: 3-Indole inhibits lung cancer growth by apoptosis. Here, the growth inhibition mechanism besides apoptosis was further characterized. Materials and Methods: The Comet assay was used to examine 3-indole-induced DNA damage. Cell cycle distribution and protein expression were analyzed using flow cytometry, Western blotting and immunohistochemistry in cell and animal models. Results: 3-Indole induced dose-dependent DNA damage, which was reversed by reactive oxygen species (ROS) inhibitor in lung cancer cells. Cell cycle G 1 arrest was observed in the 3-indole-treated cells. DNA damage-responsive proteins involved in the ataxia telangiectasia mutated/ataxia telangiectasia and Rad3-related (ATM/ATR) pathway and G1 regulation proteins such as p21 and SMA- and MAD-related protein 3 (SMAD3) were induced in the cell models. The altered expression of ATM, ATR, checkpoint kinase 2 (CHK2), and cell division cycle 25 homolog A (CDC25A) were confirmed in xenograft models. Importantly, the 3-indole-induced ATM/ATR and transforming growth factor (TGF)-β/SMAD pathways were attenuated by ROS inhibitor. Conclusion: 3-Indole causes DNA damage and triggers ATM/ATR and SMAD3 signaling pathways to arrest lung cancer cells at the G1-phase.

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