title: Antiproliferative activity and therapeutic implications of potassium tris(4-methyl-1-pyrazolyl) borohydride in hepatocellular carcinoma.
abstract: 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 (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. 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-1α 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.
authors.affiliation: Shanghai Key Laboratory of Chemical Biology, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Huangtao
authors.initials: H
authors.lastname: Jin
authors.affiliation: Shanghai Key Laboratory of Chemical Biology, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Zhongyu
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Key Laboratory of Pesticide & Chemical Biology of Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, China. Electronic address: dfli@mail.ccnu.edu.cn.
authors.forename: Dongfeng
authors.initials: D
authors.lastname: Li
authors.affiliation: Shanghai Key Laboratory of Chemical Biology, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China. Electronic address: huangjin@ecust.edu.cn.
authors.forename: Jin
authors.initials: J
authors.lastname: Huang
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D001896:Boron Compounds / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy*; D015394:Molecular Structure; D011720:Pyrazoles / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D001896:Boron Compounds; D011720:Pyrazoles; C000588561:tris(4-methyl-1-pyrazolyl)borohydride
keywords: Hepatocellular carcinoma; Iron chelator; Potassium tris-(4-methyl-1-pyrazolyl)-borohydride; Reactive oxygen species