A new Prenylated Flavonoid induces G0/G1 arrest and apoptosis through p38/JNK MAPK pathways in Human Hepatocellular Carcinoma cells.
A new Prenylated Flavonoid induces G0/G1 arrest and apoptosis through p38/JNK MAPK pathways in Human Hepatocellular Carcinoma cells.
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一种新的异戊二烯化类黄酮通过 p38/JNK MAPK 通路诱导人肝癌细胞 G0/G1 停滞和细胞凋亡
DOI：
10.1038/s41598-017-05955-0
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发表时间：
2017-07-18
影响因子：
4.6
通讯作者：
Song S
中科院分区：
文献类型：
--
作者：
Wang D;Sun Q;Wu J;Wang W;Yao G;Li T;Li X;Li L;Zhang Y;Cui W;Song S
已被证明具有包括抗肿瘤作用在内的多种生物活性。从金边瑞香中分离得到1个新的瑞香酮D(1)和4个已知的(2-5)戊烯基黄酮类化合物。结果表明，瑞香酮D对癌细胞有明显的抑制作用，但对人正常细胞无明显的细胞毒作用。机制上，瑞香酮D可诱导Hep3B和HepG2细胞G0/G1期停滞和凋亡，降低细胞周期蛋白E1、CDK2和CDK4的表达，促进caspase3和PARP的裂解。瑞香酮D使p38磷酸化水平升高，JNK磷酸化水平减弱。进一步研究表明，SB203580部分逆转了瑞香酮D诱导的G0/G1期停滞和细胞凋亡。加入SP600125可增加caspase3和PARP的裂解，但不影响G0/G1期停滞。此外，体内研究表明瑞香酮D通过抑制肿瘤细胞的增殖而明显抑制裸鼠移植瘤的生长，而对体重和病理特征无明显影响。综上所述，新化合物通过p38和JNK MAPK途径选择性地抑制肝癌细胞的增殖，提示其作为一种新型的天然抗肝癌药物的潜力。
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.
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影响因子：
2.8
作者：
Hirsch, Gabriela E.;Parisi, Mariana M.;Guma, Fatima T. C. R.
通讯作者：
Guma, Fatima T. C. R.
影响因子：
5.3
作者：
Lenczowski, JM;Dominguez, L;Ashwell, JD
通讯作者：
Ashwell, JD
作为药物先导化合物的天然内过氧化物
影响因子：
4.1
作者：
Bu, Ming;Yang, Burton B.;Hu, Liming
通讯作者：
Hu, Liming
DOI：
10.1016/j.nano.2016.02.013
发表时间：
2016-08-01
影响因子：
5.4
作者：
Hoda, Muddasarul;Pajaniradje, Sankar;Rajagopalan, Rukkumani
通讯作者：
Rajagopalan, Rukkumani
影响因子：
5.1
作者：
Gao, Suyu;Sun, Dejuan;Chen, Lixia
通讯作者：
Chen, Lixia