Ha-ras(Val12) oncogene increases susceptibility of NIH/3T3 cells to lovastatin

Meng Yao Chang, Ming Shiou Jan, Shen Jeu Won, Hsiao-Sheng Liu

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

This study demonstrates that Ha-ras(Val12) oncogene overexpression sensitizes NIH/3T3 fibroblasts to lovastatin (LOV) cytotoxicity. This sensitization is through apoptosis, which was characterized by increasing CPP32 (caspase-3) activity and DNA fragmentation. Bcl-2 overexpression increased the resistance of the Ha-ras transformants to LOV and rescued the cells from apoptosis, further confirming that the LOV-sensitive cells died of apoptosis. Further analysis showed that Ha-ras activity inversely correlated with WAF1 activity. LOV treatment suppressed Ha-ras activity but induced WAF1 activity and disrupted the cell population in G0/G1 and S phases. The Ha-ras transformants expressing either dominant negative Ras(Asn17) or Raf-1(CB4) showed reverted susceptibility to LOV. These data confirm the involvement of Ras and demonstrate that Raf-1 signalling is required for LOV-induced cell death. Taken together, the possible action of LOV-induced apoptosis is through suppressing Ha-ras activity and increasing WAF1 activity, which alters cell cycle progression and finally activates suppressed apoptotic pathway in a Fas/Fas-L- and p53-independent fashion.

Original languageEnglish
Pages (from-to)62-68
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume248
Issue number1
DOIs
Publication statusPublished - 1998 Jul 9

Fingerprint

Lovastatin
NIH 3T3 Cells
ras Genes
Apoptosis
Cells
Cell Cycle Resting Phase
G1 Phase
DNA Fragmentation
Cell death
Fibroblasts
Cytotoxicity
S Phase
Caspase 3
Cell Cycle
Cell Death
DNA
Population

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

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title = "Ha-ras(Val12) oncogene increases susceptibility of NIH/3T3 cells to lovastatin",
abstract = "This study demonstrates that Ha-ras(Val12) oncogene overexpression sensitizes NIH/3T3 fibroblasts to lovastatin (LOV) cytotoxicity. This sensitization is through apoptosis, which was characterized by increasing CPP32 (caspase-3) activity and DNA fragmentation. Bcl-2 overexpression increased the resistance of the Ha-ras transformants to LOV and rescued the cells from apoptosis, further confirming that the LOV-sensitive cells died of apoptosis. Further analysis showed that Ha-ras activity inversely correlated with WAF1 activity. LOV treatment suppressed Ha-ras activity but induced WAF1 activity and disrupted the cell population in G0/G1 and S phases. The Ha-ras transformants expressing either dominant negative Ras(Asn17) or Raf-1(CB4) showed reverted susceptibility to LOV. These data confirm the involvement of Ras and demonstrate that Raf-1 signalling is required for LOV-induced cell death. Taken together, the possible action of LOV-induced apoptosis is through suppressing Ha-ras activity and increasing WAF1 activity, which alters cell cycle progression and finally activates suppressed apoptotic pathway in a Fas/Fas-L- and p53-independent fashion.",
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Ha-ras(Val12) oncogene increases susceptibility of NIH/3T3 cells to lovastatin. / Chang, Meng Yao; Jan, Ming Shiou; Won, Shen Jeu; Liu, Hsiao-Sheng.

In: Biochemical and Biophysical Research Communications, Vol. 248, No. 1, 09.07.1998, p. 62-68.

Research output: Contribution to journalArticle

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