title: Up regulation of Bax and down regulation of Bcl2 during 3-NC mediated apoptosis in human cancer cells.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Alborz University of Medical Sciences, Karaj, Iran ; Baqiyatallah University of Medical Sciences (BMSU), Tehran, Iran.
authors.forename: Mohammad Hassan
authors.initials: MH
authors.lastname: Naseri
authors.affiliation: Department of Biology, Faculty of Natural Science, University of Tabriz, Tabriz, Iran.
authors.forename: Majid
authors.initials: M
authors.lastname: Mahdavi
authors.affiliation: Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.
authors.forename: Jamshid
authors.initials: J
authors.lastname: Davoodi
authors.affiliation: Department of Biology, Central Tehran Branch, Islamic Azad University, Tehran, Iran.
authors.forename: Saeed Hesami
authors.initials: SH
authors.lastname: Tackallou
authors.affiliation: Alborz University of Medical Sciences, Karaj, Iran.
authors.forename: Mahdi
authors.initials: M
authors.lastname: Goudarzvand
authors.affiliation: Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.
authors.forename: Shima Hallaj
authors.initials: SH
authors.lastname: Neishabouri
keywords: 3-NC; 4-aryl-4H-chromenes; Apoptosis; Bax; Bcl2