文献类型：期刊文献

英文题名：Antiproliferative activity and therapeutic implications of potassium tris(4-methyl-1-pyrazolyl) borohydride in hepatocellular carcinoma

作者：Jin, Huangtao[1];Xu, Zhongyu[1];Li, Dongfeng[2];Huang, Jin[1]

机构：[1]E China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai Key Lab Chem Biol, Shanghai 200237, Peoples R China;[2]Cent China Normal Univ, Coll Chem, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China

年份：2014

卷号：213

起止页码：69

外文期刊名：CHEMICO-BIOLOGICAL INTERACTIONS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000335281200009)】；

基金：This work is supported by the National Natural Science Foundation of China (81102420), the Shanghai Committee of Science and Technology (Grant 11DZ2260600), and the Fundamental Research Funds for the Central Universities.

语种：英文

外文关键词：Potassium tris-(4-methyl-1-pyrazolyl)-borohydride; Hepatocellular carcinoma; Iron chelator; Reactive oxygen species

摘要：The study of iron chelators as cancer chemotherapeutic agents is still in its infancy. Accordingly, there is a need to optimize new chelating molecules for iron chelation therapy and cancer treatment. Previous studies have demonstrated that the ligand tris(1-pyrazolyl) borohydride and its derivates were able to chelate ferrous iron, but very little research focused on their biological properties and applications in cancer treatment. So, in this study, several boron-pyrazole derivatives were chosen for the examination of their effects on the proliferation of human hepatocellular carcinoma (HCC) cell lines. The results suggested that potassium tris(4-methyl-1-pyrazolyl) borohydride (I(KTp(4-Me)) exhibited the most potent anti-tumor activities among the candidates. Hence, the antiproliferative activity and the iron chelating capacity of the iron chelator KTp(4-Me) in HCC cell lines HepG2 and Hep3B were characterized. 1 KTp(4-Me) could disrupt cell iron uptake and affect signaling pathways of iron regulation in HCC cell lines and induced the expression of TfR1 and HIF-1 alpha, in a concentration-dependent manner, which was a typical cell response to iron deficiency. Moreover, KTp(4-Me) arrested cell cycle in S phase and induced cell apoptosis in both Hep3B and HepG2 cells. Overall, our results provide a promising starting point and the possibility of the future development and applications of KTp(4-Me) in HCC therapy. (c) 2014 Elsevier Ireland Ltd. All rights reserved.