title: Combination of chrysin and cisplatin promotes the apoptosis of Hep G2 cells by up-regulating p53.
abstract: Cisplatin is a chemotherapy drug commonly used for the treatment of human cancers, however, drug resistance poses a major challenge to clinical application of cisplatin in cancer therapy. Recent studies have shown that chrysin, a natural flavonoid widely found in various plants and foods, demonstrated effective anti-cancer activity. In the present study, we found that the combination chrysin and cisplatin significantly enhanced the apoptosis of Hep G2 cancer cells. Combination of chrysin and cisplatin increased the phosphorylation and accumulation of p53 through activating ERK1/2 in Hep G2 cells, which led to the overexpression of the pro-apoptotic proteins Bax and DR5 and the inhibition of the anti-apoptotic protein Bcl-2. In addition, combination of chrysin and cisplatin promoted both extrinsic apoptosis by activating caspase-8 and intrinsic apoptosis by increasing the release of cytochrome c and activating caspase-9 in Hep G2 cells. Our results suggest that combination of chrysin and cisplatin is a promising strategy for chemotherapy of human cancers that are resistant to cisplatin.
authors.affiliation: Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, 1838 Northern Guangzhou Avenue, Guangzhou, Guangdong Province 510515, PR China; Center for Disease Control and Prevention of Guangdong Province, 160 Qunxian Road, Dashi, Panyu District, Guangzhou, Guangdong Province 511430, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Center for Disease Control and Prevention of Guangdong Province, 160 Qunxian Road, Dashi, Panyu District, Guangzhou, Guangdong Province 511430, PR China.
authors.forename: Jun-Ming
authors.initials: JM
authors.lastname: Huang
authors.affiliation: Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Institute of Stomatological Research, Sun Yat-sen University, 56, Ling Yuan Xi Road, Guangzhou, Guangdong Province 510055, PR China.
authors.forename: Jian-Ning
authors.initials: JN
authors.lastname: Wang
authors.affiliation: Center for Disease Control and Prevention of Guangdong Province, 160 Qunxian Road, Dashi, Panyu District, Guangzhou, Guangdong Province 511430, PR China.
authors.forename: Xi-Kun
authors.initials: XK
authors.lastname: Xiong
authors.affiliation: Center for Disease Control and Prevention of Guangdong Province, 160 Qunxian Road, Dashi, Panyu District, Guangzhou, Guangdong Province 511430, PR China. Electronic address: xfenyang@163.com.
authors.forename: Xing-Fen
authors.initials: XF
authors.lastname: Yang
authors.affiliation: Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, 1838 Northern Guangzhou Avenue, Guangzhou, Guangdong Province 510515, PR China. Electronic address: feizoudean@sina.com.
authors.forename: Fei
authors.initials: F
authors.lastname: Zou
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005419:Flavonoids / Q000008:administration & dosage / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D045325:HCT116 Cells / Q000187:drug effects / Q000473:pathology; D056945:Hep G2 Cells / Q000187:drug effects / Q000473:pathology; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494826:BAX protein, human; D005419:Flavonoids; D019253:Proto-Oncogene Proteins c-bcl-2; D018124:Receptors, Tumor Necrosis Factor; C114109:TNFRSF21 protein, human; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C043561:chrysin; D012694:Serine; D048049:Extracellular Signal-Regulated MAP Kinases; D020169:Caspases; D002945:Cisplatin
keywords: Apoptosis; Cancer; Chrysin; Cisplatin; ERK1/2; p53