一种新的异戊二烯黄酮通过人肝细胞癌细胞中的p38 / JNK MAPK途径诱导G0 / G1阻滞和凋亡。,Scientific Reports

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一种新的异戊二烯黄酮通过人肝细胞癌细胞中的p38 / JNK MAPK途径诱导G0 / G1阻滞和凋亡。
Scientific Reports ( IF 3.8 ) Pub Date : 2017-07-18 , DOI: 10.1038/s41598-017-05955-0
Di Wang , Qian Sun , Jie Wu , Wei Wang , Guodong Yao , Tianyang Li , Xue Li , Lingzhi Li , Yan Zhang , Wei Cui , Shaojiang Song

烯丙基化的类黄酮已被证明具有多种生物活性，包括抗肿瘤作用。从瑞香瑞香中分离出一种新的瑞香黄酮D（1）和四种已知的（2-5）异戊烯基黄酮。它们的细胞毒性活性表明，达芬尼拉酮D显着抑制癌细胞的增殖，但对人正常细胞没有明显的细胞毒性。从机理上讲，达芬太尼D诱导G0 / G1阻滞和凋亡，降低细胞周期蛋白E1，CDK2和CDK4的表达，并促进Hep3B和HepG2细胞中caspase 3和PARP的裂解。同时，daphnegiravone D增加了磷酸化的p38的水平，并减弱了磷酸化的JNK。进一步的研究表明，SB203580部分逆转了达芙妮拉酮D诱导的G0 / G1阻滞和凋亡。将SP600125添加到两个细胞系中均增加了半胱天冬酶3和PARP的裂解，但不影响G0 / G1阻滞。此外，体内研究表明，daphnegiravone D通过抑制肿瘤细胞的增殖而明显抑制裸鼠异种移植模型中的肿瘤生长，而对体重或病理特征没有明显影响。综上所述，该新化合物通过p38和JNK MAPK途径选择性抑制肝癌细胞的增殖，表明其具有作为新型天然抗肝细胞癌药物的潜力。对体重或病理特征无明显影响。综上所述，该新化合物通过p38和JNK MAPK途径选择性抑制肝癌细胞的增殖，表明其具有作为新型天然抗肝细胞癌药物的潜力。对体重或病理特征无明显影响。综上所述，该新化合物通过p38和JNK MAPK途径选择性抑制肝癌细胞的增殖，表明其具有作为新型天然抗肝细胞癌药物的潜力。

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A new Prenylated Flavonoid induces G0/G1 arrest and apoptosis through p38/JNK MAPK pathways in Human Hepatocellular Carcinoma cells.

Prenylated flavonoids have been demonstrated to possess diverse bioactivities including antitumor effects. One new, daphnegiravone D (1), and four known (2-5) prenylated flavonoids were isolated from Daphne giraldii. Their cytotoxic activities revealed that daphnegiravone D markedly inhibited the proliferation of cancer cells, but had no apparent cytotoxicity on human normal cells. Mechanistically, daphnegiravone D induced G0/G1 arrest and apoptosis, reduced the expression of cyclin E1, CDK2 and CDK4, and promoted the cleavage of caspase 3 and PARP in Hep3B and HepG2 cells. Meanwhile, daphnegiravone D increased the level of phosphorylated p38 and attenuated phosphorylated JNK. Further studies indicated that SB203580 partially reversed daphnegiravone D-induced G0/G1 arrest and apoptosis. The addition of SP600125 to both cell lines increased the cleavage of caspase 3 and PARP, but did not affect the G0/G1 arrest. Besides, in vivo studies demonstrated that daphnegiravone D obviously inhibited tumor growth in a nude mouse xenograft model through suppressing the proliferation of tumor cells, without significant effect on body weight or pathology characteristics. Taken together, the new compound selectively inhibited the proliferation of hepatoma cells via p38 and JNK MAPK pathways, suggesting its potential as a novel natural anti-hepatocellular carcinoma agent.

更新日期：2017-07-19

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