DNA mismatch repair as an effector for promoting phorbol ester-induced apoptotic DNA damage and cell killing: Implications in tumor promotion

Ching Tai Lin, Wei Hsin Lin, Kuan Der Lee, Pay Yu Tzeng

研究成果: 雜誌貢獻 › 文章

8 引文 (Scopus)

摘要

Phorbol ester was known to activate protein kinase C (PKC) and exert numerous cellular effects, including proliferation, apoptosis, and oncogenic transformation. How phorbol ester stimulates both apoptosis and tumor promotion is not clear. Here DNA mismatch repair (MMR)-proficient human colon cancer cells (DLD-1+Ch2; hMSH6+) treated with l2-O-tetradecanoylphorbol-13- acetate (TPA) undergo rapid cell death, which is significantly abolished by staurosporine (PKC inhibitor) or antioxidant, compared with the paired MMR-deficient (DLD-1; hMSH6-) cells. Induction of reactive oxygen species (ROS) by TPA is shown to be one of downstream effectors required, but not sufficient, for cell killing as it is also observed in DLD-1 cells. Strikingly, DLD-1+Ch2 cells selected for resistance to TPA are found to lose the expression of hMSH6. Treatment of TPA-resistant DLD4+Ch2 cells with 5-aza-2′-deoxycytidine, not only restores hMSH6 expression but also resensitizes TPA-resistant cells to TPA, suggesting that expression of hMSH6 is transcriptionally silenced by cytosine methylation confirmed directly by bisulfite sequencing. Knockdown hMSH6 or hPMS2 with siRNA in DLD-1+Ch2 cells resulted in more resistant to TPA-induced cell killing, further suggesting that MMR proteins involve in TPA or ROS-induced cell killing. Results suggest that deficiency in MMR could promote tumorigenesis by inhibiting apoptotic responses to ROS-mediated DNA damages as ROS are continuously produced as a byproduct of normal metabolism.
原文英語
頁（從 - 到）1776-1784
頁數9
期刊International Journal of Cancer
卷119
發行號8
DOIs
出版狀態已發佈 - 十月 15 2006
對外發佈Yes

指紋

DNA Mismatch Repair
Phorbol Esters
DNA Damage
Tetradecanoylphorbol Acetate
Neoplasms
Reactive Oxygen Species
decitabine
Protein Kinase C
Apoptosis
Staurosporine
Protein C Inhibitor
Cytosine
Protein Kinase Inhibitors
Colonic Neoplasms
Methylation
Small Interfering RNA
Carcinogenesis
Cell Death
Antioxidants

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

引用此文

DNA mismatch repair as an effector for promoting phorbol ester-induced apoptotic DNA damage and cell killing : Implications in tumor promotion. / Lin, Ching Tai; Lin, Wei Hsin; Lee, Kuan Der; Tzeng, Pay Yu.

於: International Journal of Cancer, 卷 119, 編號 8, 15.10.2006, p. 1776-1784.

研究成果: 雜誌貢獻 › 文章

Lin, CT, Lin, WH, Lee, KD & Tzeng, PY 2006, 'DNA mismatch repair as an effector for promoting phorbol ester-induced apoptotic DNA damage and cell killing: Implications in tumor promotion', International Journal of Cancer, 卷 119, 編號 8, 頁 1776-1784. https://doi.org/10.1002/ijc.22068
Lin CT, Lin WH, Lee KD, Tzeng PY. DNA mismatch repair as an effector for promoting phorbol ester-induced apoptotic DNA damage and cell killing: Implications in tumor promotion. International Journal of Cancer. 2006 10月 15;119(8):1776-1784. https://doi.org/10.1002/ijc.22068
Lin, Ching Tai ; Lin, Wei Hsin ; Lee, Kuan Der ; Tzeng, Pay Yu. / DNA mismatch repair as an effector for promoting phorbol ester-induced apoptotic DNA damage and cell killing : Implications in tumor promotion. 於: International Journal of Cancer. 2006 ; 卷 119, 編號 8. 頁 1776-1784.
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