A new brominated chalcone derivative suppresses the growth of gastric cancer cells in vitro and in vivo involving ROS mediated up-regulation of DR5 and 4 expression and apoptosis.
A new brominated chalcone derivative suppresses the growth of gastric cancer cells in vitro and in vivo involving ROS mediated up-regulation of DR5 and 4 expression and apoptosis.
复制标题
一种新的溴化查耳酮衍生物在体外和体内抑制胃癌细胞的生长，涉及ROS介导的DR5和4表达上调以及细胞凋亡
DOI：
10.1016/j.taap.2016.08.023
复制
发表时间：
2016-10-15
影响因子：
3.8
通讯作者：
Liu HM
中科院分区：
文献类型：
--
作者：
Zhang S;Li T;Zhang Y;Xu H;Li Y;Zi X;Yu H;Li J;Jin CY;Liu HM
设计、合成了一系列新的20个溴化查尔酮衍生物，并研究了它们对四种癌细胞株(EC109、SKNSH、HepG2、MGC803)的生长抑制作用。其中化合物19的化学名称为H72，对胃癌细胞株(即MGC803、HGC27、SGC7901)的抑制作用最强，IC50为3.57~5.61μ，对非恶性胃上皮细胞GES-1的杀伤作用较弱。H72处理MGC803和HGC27诱导产生的ROS导致caspase 9/3级联激活和线粒体介导的细胞凋亡。H72还上调DR5、DR4和BimEL的表达，下调Bid、Bclxl和XIAP的表达。ROS清除剂N-乙酰半胱氨酸(NAC)可完全阻断H72对MGC803细胞的上述作用。在异种移植小鼠模型中，H72在体内显著抑制MGC803细胞的生长，而没有观察到毒性。这些结果表明，H72是一种铅溴化查尔酮衍生物，在预防和治疗胃癌方面值得进一步研究。
A new series of 20 brominated chalcone derivatives were designed, synthesized, and investigated for their effects against the growth of four cancer cell lines (EC109, SKNSH, HepG2, MGC803). Among them, compound 19 which given chemical name of H72, was the most potent one on gastric cancer cell lines (i.e. MGC803, HGC27, SGC7901) with IC50s ranged from 3.57 to 5.61 μM. H72 exhibited less cytotoxicity to non-malignant gastric epithelial cells GES-1. H72 treatment of MGC803 and HGC27 induced generation of reactive oxygen species (ROS) leading to activation of caspase 9/3 cascade and mitochondria mediated apoptosis. H72 also up-regulated the expression of DR5, DR4 and BimEL, and down-regulated the expression of Bid, Bcl-xL, and XIAP. N-acetyl cysteine (NAC), a ROS scavenger completely blocked these effects of H72 in MGC803 cells. Intraperitoneal administration of H72 significantly inhibited the growth of MGC803 cells in vivo in a xenograft mouse model without observed toxicity. These results indicated that H72 is a lead brominated chalcone derivate and deserves further investigation for prevention and treatment of gastric cancer.
登录
查看更多内容
影响因子：
7.2
作者：
Veenman, Leo;Alten, Julia;Linnemannstons, Karen;Shandalov, Yulia;Zeno, Sivan;Lakomek, Max;Gavish, Moshe;Kugler, Wilfried
通讯作者：
Kugler, Wilfried
影响因子：
5.4
作者：
Jeong, Seong-Yun;Han, Min Ho;Choi, Yung Hyun
通讯作者：
Choi, Yung Hyun
影响因子：
3.2
作者：
Park, Cheol;Jin, Cheng-Yun;Choi, Yung Hyun
通讯作者：
Choi, Yung Hyun
影响因子：
4.8
作者：
Gupta, Subash C.;Francis, Sajin K.;Aggarwal, Bharat B.
通讯作者：
Aggarwal, Bharat B.
影响因子：
254.7
作者：
Siegel, Rebecca;Ma, Jiemin;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin