Up regulation of Bax and down regulation of Bcl2 during 3-NC mediated apoptosis in human cancer cells

Cancer Cell International

Shima Hallaj Neishabouri³  Mahdi Goudarzvand⁵  Saeed Hesami Tackallou¹  Jamshid Davoodi³  Majid Mahdavi²  Mohammad Hassan Naseri⁴ 

[1] Department of Biology, Central Tehran Branch, Islamic Azad University, Tehran, Iran;Department of Biology, Faculty of Natural Science, University of Tabriz, Tabriz, Iran;Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran;Baqiyatallah University of Medical Sciences (BMSU), Tehran, Iran;Alborz University of Medical Sciences, Karaj, Iran

关键词: 3-NC;    Bcl2;    Bax;    4-aryl-4H-chromenes;    Apoptosis;   

Others  :  1219350
DOI  :  10.1186/s12935-015-0204-2

 received in 2014-12-09, accepted in 2015-05-11,  发布年份 2015

【 摘 要 】

Background

Recently, we have reported the induction of apoptosis by 2-amino-4-(3-nitrophenyl)-3-cyano-7-(dimethylamino)-4H-chromene (3-NC) in HepG2, T47D and HCT116 cells with low nano molar IC50 values. In this study, anti-proliferative effects of modified 4-aryle-4H-chromenes derivatives; 2-amino-4-(3-bromophenyl)-3-cyano-7-(dimethylamino)-4H-chromene (3-BC), 2-amino-4-(3-trifluoromethylphenyl)-3-cyano-7-(dimethylamino)-4H-chromene (3-TFC) and 2-amino-4-(4,5-methylenedioxyphenyl)-3-cyano-7-(dimethylamino)-4H-chromene (4, 5-MC) were investigated in three human cancer cell lines. Compared to 3-NC none of the compounds displayed better anti-proliferative effect, although 3-BC appeared somewhat similar. Therefore 3-NC was selected for further studies.

Methods and results

Treatment of HepG2, T47D and HCT116 cells with this compound induced apoptosis as visualized by fluorescence microscopic study of Hoechst 33258 stained cells. Induction of apoptosis was quantified by Annexin V/PI staining using flow cytometry.

Western blot analysis also revealed that 3-NC down-regulated the expression of anti-apoptotic protein Bcl2 and up-regulated pro-apoptotic protein Bax, in all of the cell lines. Nonetheless, HepG2 cell line was the most responsive to 3-NC as Bax and Bcl2 showed the most dramatic up and down regulation.

Conclusion

Our previous finding that 3-NC down regulates Inhibitor of Apoptosis Proteins (IAPs) and the present observation that Bax is upregulated and Bcl2 is down regulated upon 3-NC treatment, this chromene derivative has the potential to overcome chemotherapy resistance caused by up regulation of these proteins.

【 授权许可】

   
2015 Naseri et al.; licensee BioMed Central.

【 图 表 】

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