Department of Biochemistry, University of Madras, Guindy Campus, Chennai, India.
Toxicol Appl Pharmacol. 2011 Feb 15;251(1):85-94. doi: 10.1016/j.taap.2010.12.004. Epub 2010 Dec 15.
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.
类黄酮具有很强的抗氧化和抗癌化学预防作用。白杨素（5,7-二羟基黄酮）自然存在于许多植物、蜂蜜和蜂胶中。在体外，白杨素作为一种通用抗氧化剂，可引起细胞周期停滞并促进细胞死亡。然而，白杨素抑制癌细胞生长的机制以及被激活的亚细胞途径仍知之甚少。本研究在雄性 Wistar 大鼠中研究了膳食补充白杨素对二乙基亚硝胺（DEN）诱导的早期肝癌发生过程中的增殖和凋亡的影响。为了诱导肝癌发生，大鼠接受 DEN 注射（腹腔内，200mg/kg），每 15 天一次，共三次。白杨素（250mg/kg 体重）的口服剂量每周三次，共 3 周，在 DEN 最后一次给药后 1 周开始。通过实时定量 PCR 评估 COX-2、NFkB p65、p53、Bcl-xL 和 β-arrestin-2 的 mRNA 表达变化。通过 Western blot 测量蛋白水平的变化。白杨素给药显著（P<0.001）减少了形成的结节数量和大小。此外，还观察到血清中 AST、ALT、ALP、LDH 和 γGT 活性显著降低（P<0.01）。COX-2 和 NFkB p65 的表达在 mRNA 和蛋白水平均显著降低，而 p53、Bax 和 caspase 3 的表达增加。同样，β-arrestin 和抗凋亡标志物 Bcl-xL 的水平也降低。这些发现表明，白杨素发挥整体肝保护作用，其化学预防活性与早期肝癌发生过程中 p53 介导的细胞凋亡有关。
