Citrus platymamma Hort.et Tanaka is an indigenous fruit of Jeju island in Korea. In this study the bioactivity of C. platymamma flavonoids were evaluated on human hepatoma Hep3B cell lines. Eleven flavonoids were identified from the peels of C. platymamma Hort.et Tanaka through high-performance liquid chromatography-Tandem mass spectrometry and the anticancer effect of these C. platymamma flavonoids on human hepatoma Hep3B were studied. Chromatin condensation was observed in Hep3B cells treated with C. platymamma flavonoids. DNA fragmentation was confirmed through agarose gel electrophoresis and TUNEL assay. An increase in the total apoptotic cells and G2/M cell cycle arrest with decreased protein expression of CDC25C, CDK1, cyclin B1 and p21 were observed in Hep3B cells treated with flavonoids of C. platymamma. Further, protein expression of Bcl-XL, Bax, caspase-3 and -9 were also modulated by C. platymamma flavonoids treatment indicating that cell death is through intrinsic apoptotic pathway. Moreover, C. platymamma flavonoids also regulated the phosphorylation of MAPKs, PI3K, and Akt in Hep3B cells. Relevant to inhibiting metastasis, C. platymamma treatment reduced wound closure of Hep3B cells and the protein expression of matrix metalloproteinase-2 and -9 were reduced in C. platymamma treated cells. The results show that C. platymamma flavonoids induce cell cycle arrest and apoptosis following activation of MAPKs and suppression of PI3K/Akt pathway which eventually inhibits cell migration in Hep3B cells. The finding provides evidence on biochemical activities of C. platymamma Hort.et Tanaka, which would be an essential agent for hepatocellular carcinoma (HCC) treatment.

译文

:Citrus platymamma Hort.et Tanaka是韩国济州岛的土特产。在这项研究中,对人肝癌Hep3B细胞系评估了C.platymamma类黄酮的生物活性。通过高效液相色谱-串联质谱法从桔梗Hor.et Tanaka的果皮中鉴定出11种黄酮,并研究了这些桔梗黄酮对人肝癌Hep3B的抗癌作用。在用衣原体C.platymamma类黄酮处理的Hep3B细胞中观察到染色质浓缩。通过琼脂糖凝胶电泳和TUNEL测定法确认了DNA片段化。在用桔梗小球藻类黄酮处理的Hep3B细胞中观察到总凋亡细胞增加和G2 / M细胞周期停滞,CDC25C,CDK1,cyclin B1和p21蛋白表达降低。此外,Bcl-XL,Bax,caspase-3和-9的蛋白表达也受到C.platymamma类黄酮处理的调节,表明细胞死亡是通过内在的凋亡途径进行的。此外,C.platymamma类黄酮还调节Hep3B细胞中MAPK,PI3K和Akt的磷酸化。与抑制转移有关,C.platymamma处理可减少Hep3B细胞的伤口闭合,并且在C.platymamma处理的细胞中基质金属蛋白酶2和-9的蛋白质表达降低。结果表明,C.platymamma类黄酮在激活MAPK和抑制PI3K / Akt通路后诱导细胞周期停滞和凋亡,从而最终抑制Hep3B细胞中的细胞迁移。该发现提供了关于白斑梭菌Hort.et Tanaka的生化活性的证据,这将是肝细胞癌(HCC)治疗的基本药物。

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