Archives of Pharmacal Research

, Volume 35, Issue 9, pp 1573–1582 | Cite as

Anti-proliferative and apoptotic effects of the derivatives from 4-aryl-4H-chromene family on human leukemia K562 cells

Research Article Drug Design and Discovery

Abstract

Previous studies suggest that 4-aryl-4H-chromenes are potent apoptosis-inducing agents in various cancer cell lines. In this study, anti-proliferative and apoptotic effects of the derivatives from 4-aryl-4H-chromene family were investigated in the human leukemia K562 cells using [3-(4,5)-dimethyl-2-thiazolyl]-2,5-diphenyl-2H-tetrazolium bromide (MTT) growth inhibition assay. 3-NC was more active among these compounds with IC50 of 65 nM and was selected for further studies. Apoptosis, as the mechanism of cell death, was investigated morphologically by Hoechst 33258 staining, cell surface expression assay of phosphatidylserine by Annexin V/PI technique, caspase-3 activation assay, as well as the formation of DNA ladder. The K562 cells underwent apoptosis upon a single dose (at IC50 value) of the compound, and also increased caspase-3 activity by more than 2.3-fold, following a 72 h treatment. Caspase-9 was also activated which could be detected 48 hours post-treatment. Furthermore, Western blot analysis revealed that the treatment with the compound down-regulated the expression of certain IAP protein, including survivin. These data further suggest that these derivatives from 4-aryl-4H-chromene may provide a novel therapeutic approach for the treatment of leukemia.

Key words

Apoptosis 4-Aryl-4H-chromenes Caspase-3 K562 cells Survivin 

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Copyright information

© The Pharmaceutical Society of Korea and Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  1. 1.Department of Biology, Sanandaj BranchIslamic Azad UniversitySanandajIran
  2. 2.Department of Biology, Faculty of Natural ScienceUniversity of TabrizTabrizIran
  3. 3.Research Center for Gastroenterology and Liver DiseasesShahid Beheshti University of Medical SciencesTehranIran
  4. 4.Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research CenterTehran University of Medical SciencesTehranIran

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