title: Chrysin abrogates early hepatocarcinogenesis and induces apoptosis in N-nitrosodiethylamine-induced preneoplastic nodules in rats.
abstract: Flavonoids possess strong anti-oxidant and cancer chemopreventive activities. Chrysin (5,7-dihydroxyflavone) occurs naturally in many plants, honey, and propolis. In vitro, chrysin acts as a general anti-oxidant, causes cell cycle arrest and promotes cell death. However, the mechanism by which chrysin inhibits cancer cell growth and the subcellular pathways activated remains poorly understood. Effect of dietary supplementation with chrysin on proliferation and apoptosis during diethylnitrosamine (DEN)-induced early hepatocarcinogenesis was investigated in male Wistar rats. To induce hepatocarcinogenesis, rats were given DEN injections (i.p., 200 mg/kg) three times at a 15 day interval. An oral dose of chrysin (250 mg/kg bodyweight) was given three times weekly for 3 weeks, commencing 1 week after the last dose of DEN. Changes in the mRNA expression of COX-2, NFkB p65, p53, Bcl-xL and β-arrestin-2 were assessed by quantitative real-time PCR. Changes in the protein levels were measured by western blotting. Chrysin administration significantly (P<0.001) reduced the number and size of nodules formed. Also, a significant (P<0.01) reduction in serum activities of AST, ALT, ALP, LDH and γGT was noticed. Expression of COX-2 and NFkB p65 was significantly reduced whereas that of p53, Bax and caspase 3 increased at the mRNA and protein levels. Likewise, a decrease in levels of β-arrestin and the anti-apoptotic marker Bcl-xL was also noted. These findings suggest that chrysin exerts global hepato-protective effect and its chemopreventive activity is associated with p53-mediated apoptosis during early hepatocarcinogenesis.
authors.affiliation: Department of Biochemistry, University of Madras, Guindy Campus, Chennai, India.
authors.forename: Mahaboob S
authors.initials: MS
authors.lastname: Khan
authors.forename: Halagowder
authors.initials: H
authors.lastname: Devaraj
authors.forename: Niranjali
authors.initials: N
authors.lastname: Devaraj
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D019390:Arrestins / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D001835:Body Weight; D018797:Cell Cycle Proteins / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004052:Diethylnitrosamine; D005419:Flavonoids / Q000494:pharmacology*; D051549:Glutathione S-Transferase pi / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D009929:Organ Size; D011230:Precancerous Conditions / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D051996:Transcription Factor RelA / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins
chemical_list: D016588:Anticarcinogenic Agents; D051017:Apoptosis Regulatory Proteins; C000605257:Arrb2 protein, rat; D019390:Arrestins; D015415:Biomarkers; D018797:Cell Cycle Proteins; D005419:Flavonoids; C498145:Rela protein, rat; D051996:Transcription Factor RelA; D016159:Tumor Suppressor Protein p53; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins; C043561:chrysin; D004052:Diethylnitrosamine; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D051549:Glutathione S-Transferase pi; C496558:Gstp1 protein, rat