Anti-proliferative and apoptotic effects of the derivatives from 4-aryl-4H-chromene family on human leukemia K562 cells.
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.
Department of Biology, Sanandaj Branch, Islamic Azad University, Sanandaj, Iran. aryapour@ibb.ut.ac.ir
Hassan
H
Aryapour
Majid
M
Mahdavi
Seyed Reza
SR
Mohebbi
Mohammad Reza
MR
Zali
Alireza
A
Foroumadi
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001578:Benzopyrans / Q000737:chemistry* / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D053144:Cell Nucleus Shape / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D015195:Drug Design; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D020128:Inhibitory Concentration 50; D007938:Leukemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009363:Neoplasm Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship; D000077022:Survivin; D015854:Up-Regulation / Q000187:drug effects
C578978:2-amino-4-(3-nitrophenyl)-3-cyano-7-(dimethylamino)-4H-chromene; D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D001578:Benzopyrans; D051034:Inhibitor of Apoptosis Proteins; D009363:Neoplasm Proteins; D000077022:Survivin; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9