Antitumor activity of a novel bis-aziridinylnaphthoquinone (AZ4) mediating cell cycle arrest and apoptosis in non-small cell lung cancer cell line NCI-H460

Kou Gea Shyu, Sheng Tung Huang, Hsien Shou Kuo, Wen Pin Cheng, Yuh Ling Lin

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Aim: The cytotoxic activities of a series of bis-aziridinylnaphthoquinone, AZ1 to AZ4, on human lung carcinoma cell lines, H460, and normal lung cells fibroblast cell line, MRC-5, and the mechanisms of H460 cells induced by AZ4 were investigated. Methods: The MTT assay was used to determine the cell proliferation. Cell cycle was analysed by FACS. The activity of caspase 3, 8 and 9 was determined by cell-permeable fluorogenic detection system. Western blot assay was used to evaluate the regulation of cyclin B, Cdc-2, p53, p21, and the Bcl-2 protein. Results: AZ1 to AZ4 displayed various cytotoxicity activities against H460 and MRC-5 cells. Compared to those compounds, AZ4 was with the most effective agent among the 5 tested analogues at reducing H460 cell viability with an IC50 value of 1.23 μmol/L; it also exhibited weak cytotoxicity against MRC-5 cells with an IC50 value of 12.7 μmol/L. The results show that growth arrest on the G2-M phase of H460 cells induced by AZ4 for 24 h was discovered, and this might be altered with the reduced Cdc-2 protein expression of 47% at 2.0 μmol/L AZ4, but not with cyclin B protein expression. The AZ4 treated cells were then led to apoptosis after 48 h. This was associated with the activation of apoptotic enzyme caspase 3 and mediated by caspase 8, but not caspase 9 at various concentrations of AZ4 after being cultured for 48 h and 30 h, respectively. The anti-apoptotic protein (Bcl-2) expression in H460 cells altered by 39% with downregulation, and the p53 protein by 25% with upregulation after being cultured with 2.0 μmol/L AZ4 for 48 h. In a time-dependent wanrer, the expression of the p53 and p21 proteins were increased to the maximum at 24 h, and then decreased at 48. Conclusion: AZ4 represents a novel antitumor aziridinylnaphthoquinone with therapeutic potential against the non-small cell lung cancer cells.

Original languageEnglish
Pages (from-to)559-566
Number of pages8
JournalActa Pharmacologica Sinica
Volume28
Issue number4
DOIs
Publication statusPublished - Apr 2007

Fingerprint

Cell Cycle Checkpoints
Non-Small Cell Lung Carcinoma
Cells
Apoptosis
Cell Line
Cyclin B
Cytotoxicity
Proteins
Caspase 3
Caspase 9
Caspase 8
Assays
Inhibitory Concentration 50
Apoptosis Regulatory Proteins
Cell proliferation
Fibroblasts
bis-aziridinylnaphthoquinone
Lung
Cell Cycle Proteins
Enzyme Activation

Keywords

  • Apoptosis
  • Aziridinylnaphthoquinone
  • Bcl-2 protein
  • Cell cycle

ASJC Scopus subject areas

  • Chemistry(all)
  • Pharmacology

Cite this

Antitumor activity of a novel bis-aziridinylnaphthoquinone (AZ4) mediating cell cycle arrest and apoptosis in non-small cell lung cancer cell line NCI-H460. / Shyu, Kou Gea; Huang, Sheng Tung; Kuo, Hsien Shou; Cheng, Wen Pin; Lin, Yuh Ling.

In: Acta Pharmacologica Sinica, Vol. 28, No. 4, 04.2007, p. 559-566.

Research output: Contribution to journalArticle

Shyu, Kou Gea ; Huang, Sheng Tung ; Kuo, Hsien Shou ; Cheng, Wen Pin ; Lin, Yuh Ling. / Antitumor activity of a novel bis-aziridinylnaphthoquinone (AZ4) mediating cell cycle arrest and apoptosis in non-small cell lung cancer cell line NCI-H460. In: Acta Pharmacologica Sinica. 2007 ; Vol. 28, No. 4. pp. 559-566.
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abstract = "Aim: The cytotoxic activities of a series of bis-aziridinylnaphthoquinone, AZ1 to AZ4, on human lung carcinoma cell lines, H460, and normal lung cells fibroblast cell line, MRC-5, and the mechanisms of H460 cells induced by AZ4 were investigated. Methods: The MTT assay was used to determine the cell proliferation. Cell cycle was analysed by FACS. The activity of caspase 3, 8 and 9 was determined by cell-permeable fluorogenic detection system. Western blot assay was used to evaluate the regulation of cyclin B, Cdc-2, p53, p21, and the Bcl-2 protein. Results: AZ1 to AZ4 displayed various cytotoxicity activities against H460 and MRC-5 cells. Compared to those compounds, AZ4 was with the most effective agent among the 5 tested analogues at reducing H460 cell viability with an IC50 value of 1.23 μmol/L; it also exhibited weak cytotoxicity against MRC-5 cells with an IC50 value of 12.7 μmol/L. The results show that growth arrest on the G2-M phase of H460 cells induced by AZ4 for 24 h was discovered, and this might be altered with the reduced Cdc-2 protein expression of 47{\%} at 2.0 μmol/L AZ4, but not with cyclin B protein expression. The AZ4 treated cells were then led to apoptosis after 48 h. This was associated with the activation of apoptotic enzyme caspase 3 and mediated by caspase 8, but not caspase 9 at various concentrations of AZ4 after being cultured for 48 h and 30 h, respectively. The anti-apoptotic protein (Bcl-2) expression in H460 cells altered by 39{\%} with downregulation, and the p53 protein by 25{\%} with upregulation after being cultured with 2.0 μmol/L AZ4 for 48 h. In a time-dependent wanrer, the expression of the p53 and p21 proteins were increased to the maximum at 24 h, and then decreased at 48. Conclusion: AZ4 represents a novel antitumor aziridinylnaphthoquinone with therapeutic potential against the non-small cell lung cancer cells.",
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AU - Huang, Sheng Tung

AU - Kuo, Hsien Shou

AU - Cheng, Wen Pin

AU - Lin, Yuh Ling

PY - 2007/4

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N2 - Aim: The cytotoxic activities of a series of bis-aziridinylnaphthoquinone, AZ1 to AZ4, on human lung carcinoma cell lines, H460, and normal lung cells fibroblast cell line, MRC-5, and the mechanisms of H460 cells induced by AZ4 were investigated. Methods: The MTT assay was used to determine the cell proliferation. Cell cycle was analysed by FACS. The activity of caspase 3, 8 and 9 was determined by cell-permeable fluorogenic detection system. Western blot assay was used to evaluate the regulation of cyclin B, Cdc-2, p53, p21, and the Bcl-2 protein. Results: AZ1 to AZ4 displayed various cytotoxicity activities against H460 and MRC-5 cells. Compared to those compounds, AZ4 was with the most effective agent among the 5 tested analogues at reducing H460 cell viability with an IC50 value of 1.23 μmol/L; it also exhibited weak cytotoxicity against MRC-5 cells with an IC50 value of 12.7 μmol/L. The results show that growth arrest on the G2-M phase of H460 cells induced by AZ4 for 24 h was discovered, and this might be altered with the reduced Cdc-2 protein expression of 47% at 2.0 μmol/L AZ4, but not with cyclin B protein expression. The AZ4 treated cells were then led to apoptosis after 48 h. This was associated with the activation of apoptotic enzyme caspase 3 and mediated by caspase 8, but not caspase 9 at various concentrations of AZ4 after being cultured for 48 h and 30 h, respectively. The anti-apoptotic protein (Bcl-2) expression in H460 cells altered by 39% with downregulation, and the p53 protein by 25% with upregulation after being cultured with 2.0 μmol/L AZ4 for 48 h. In a time-dependent wanrer, the expression of the p53 and p21 proteins were increased to the maximum at 24 h, and then decreased at 48. Conclusion: AZ4 represents a novel antitumor aziridinylnaphthoquinone with therapeutic potential against the non-small cell lung cancer cells.

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KW - Aziridinylnaphthoquinone

KW - Bcl-2 protein

KW - Cell cycle

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