Carcinogenesis, Teratogenesis & Mutagenesis

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Effect of digitoxin on proliferation and cell cycle of NCI-H446 and A549 cells

LIU Feng,CHEN Zhitian,SHAO Kongjian,SA Benzhong   

  1. Department of Hepatobiliary Surgery, The Second Hospital of Fuzhou, Fuzhou 350007, Fujian, China
  • Received:2014-07-14 Revised:2014-10-21 Online:2015-01-31 Published:2015-01-31

Abstract:

OBJECTIVE: To investigate the effects of digitoxin on proliferation and cell cycle of human lung cancer cell lines NCI-H446 and A549,and to explore its possible mechanisms. METHODS:NCI-H446 and A549 cells were treated with digitoxin at different concentrations(10,20,40,80 and 160 nmol/L). The effect on proliferation of NCI-H446 and A549 cells were detected by MTT assay. Flow cytometry was used to test the cell cycle distribution of NCI-H446 and A549 cells. Protein expressions of Cyclin A1 and P21 in NCI-H446 and A549 cells were evaluated by Western blot. RESULTS:As compared with control group,cell proliferation was inhibited by digitoxin in a dose- and time-dependent manner(P<0.05),the IC50 value for digotoxin were 61.26 nmol/L in NCI-H446 and 110.73 nmol/L in A549 at 48 h. After 48 h treatment,the proportion of NCI-H446 and A549 cells in G0/G1 phase was decreased,while the proportion in S phase was increased. Western blot analysis showed that digitoxin could significantly up-regulate the expression of Cyclin A1 and down-regulate the expression of P21 in a dose-dependent way(P<0.05). CONCLUSION: Digitoxin could exert an the anti-proliferative effect on NCI-H446 and A549 cells and induce S phase arrest in vitro. The mechanism may be related to the expressions of proteins associated with cell cycle.

Key words: digitoxin, lung cancer, regulation of cell cycle, Cyclin A1