title: 5-Benzylidene-3,4-dihalo-furan-2-one derivatives inhibit human leukemia cancer cells through suppression of NF-κB and GSK-3β.
abstract: It has been demonstrated that PPARγ agonists effectively inhibit proliferation, metastasis as well as induce apoptosis in human cancer cell lines. In this study, twenty-two rosiglitazone analogues, 5-benzylidene-3,4- dihalo-furan-2-one derivatives, which have been identified as PPARγ agonists in our previous work, were evaluated for their antitumor effects. Among these compounds, (Z)-3,4-dibromo-5-(3-methoxy-4-((3,5,6-trimethylpyrazin-2- yl)methoxy)benzylidene)furan-2(5H)-one (6w) shows the best antitumor activity, especially against the leukemia cell line U937, resulting in significant cytotoxicity, increased apoptosis and changes in mitochondrial membrane potential. Up-regulation of pro-apoptosis-associated proteins (Bax, caspase-3 and caspase-9) and cleaved PARP as well as down-regulation of anti-apoptosis protein Bcl-2 are observed in 6w-treated U937 cells. It was shown that the antitumor effect of 6w stems from its ability to inhibit the PPARγ-dependent expression of NF-κB and GSK-3β.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, P. R. China. linjing_jnu@163.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Lin
authors.forename: Wen
authors.initials: W
authors.lastname: Hou
authors.forename: Mei-Yan
authors.initials: MY
authors.lastname: Huang
authors.forename: Ping-Hua
authors.initials: PH
authors.lastname: Sun
authors.forename: Wei-Min
authors.initials: WM
authors.lastname: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects; D005663:Furans / Q000494:pharmacology*; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D019073:HT29 Cells; D006367:HeLa Cells; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology; D020298:U937 Cells; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D005663:Furans; D016328:NF-kappa B; D047495:PPAR gamma; D019253:Proto-Oncogene Proteins c-bcl-2; D045162:Thiazolidinediones; D000077154:Rosiglitazone; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; C039281:furan