Inhibition Mechanism of Novel Pyrazolo[1,5-a]pyrazin-4(5H)-one Derivatives Against Proliferation of A549 and H322 Cancer Cells<sup>△</sup>

Shao Jin-hui; Feng Gui-hua

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Inhibition Mechanism of Novel Pyrazolo[1,5-a]pyrazin-4(5H)-one Derivatives Against Proliferation of A549 and H322 Cancer Cells^△

Chinese Medical Sciences Journal Vol. 30, Issue 4, Pages: 260-265(2015)

Orginal Article | Updated：2024-04-10

- Inhibition Mechanism of Novel Pyrazolo[1,5-a]pyrazin-4(5H)-one Derivatives Against Proliferation of A549 and H322 Cancer Cells^△
- Affiliations：
  
  1. 1Department of Medical Morphology, School of Medicine, Hubei University of Art and Science, Xiangyang 441053, Hubei, China
  2. 2Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Jinan 250100, China
- Author bio：
  
  *Corresponding author Tel: 86-710-3591126, E-mail: jhshao666@163.com
- Funds：
- DOI：
  CLC：
- Published Online：20 August 2015，
  
  Published：2015-08
- Accepted：
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Shao Jin-hui, Feng Gui-hua. Inhibition Mechanism of Novel Pyrazolo[1,5-a]pyrazin-4(5H)-one Derivatives Against Proliferation of A549 and H322 Cancer Cells^△[J]. Chinese medical sciences journal, 2015, 30(4): 260-265.
DOI：

Shao Jin-hui, Feng Gui-hua. Inhibition Mechanism of Novel Pyrazolo[1,5-a]pyrazin-4(5H)-one Derivatives Against Proliferation of A549 and H322 Cancer Cells^△[J]. Chinese medical sciences journal, 2015, 30(4): 260-265. DOI：

摘要

Abstract

Objective

To explore the inhibition mechanism and safety of pyrazolo[1

5-a]pyrazin-4(5H)-one derivatives against proliferation of human lung cancer A549 cells

H322 cells

and human umbilical vein endothelial cell (HUVEC).

Methods

Cells were treated with 40 μmol/L of the ppo3a

ppo3b

ppo3i

and 0.1% DMSO (control) for 48 hours

respectively. Apoptosis was determined by Hoechst 33258 staining assay in H322 and A549 cells. Cell cycle distribution was determined by flow cytometry analysis in A549 cell. LC3-II

p53

and heat shock protein (HSP) 70 protein levels were detected by Western blotting in A549 cells treated with ppo3b for 48 hours. The morphology and viability of HUVEC were observed by inverted microscope and sulforhodamine B (SRB) assay.

Results

Ppo3a

ppo3b

and ppo3i significantly induced apoptosis in H322 and A549 cells. A strong G1-phase arrest was concomitant with the growth inhibitory effect on A549 cells. Ppo3b effectively elevated the p53 protein level

but significantly reduced the HSP70 protein level. There were no significantly inhibitory effect on the morphology and viability of HUVEC when treated with ppo3a

ppo3b

and ppo3i.

Conclusions

ppo3a

ppo3b

and ppo3i could inhibit H322 proliferation through apoptosis and inhibit A549 through apoptosis and G1-phase arrest. The protein p53 and HSP70 might involve in the inhibition effects. These derivatives might be a clue to find effective and safe drug for lung cancers.

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references

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