title: Anticancer and Antiangiogenic Iron(II) Complexes That Target Thioredoxin Reductase to Trigger Cancer Cell Apoptosis.
abstract: Thioredoxin reductase (TrxR) is a selenoenzyme that could regulate intracellular oxidative balance and found to be overexpressed in many human tumor cells. Due to its important role in cancer progression, TrxR is becoming an attractive target in chemotherapeutic drug design. In this study, a new class of Fe(II) complexes with phenanthroline derivatives as ligands were synthesized and characterized. The mechanism of cell death induced by complex 3 revealed that the growth of cancer cells was suppressed by apoptosis and specifically inhibited the activities of TrxR. Furthermore, complex 3 exhibited brilliant antiangiogenic activity against HUVEC cells and inhibited cell migration and invasion. In addition, results of hematological analysis and H&E staining demonstrated that complex 3 has negligible toxicity on function of the major organs of mice. Taken together, this study provides a strategy for drug design to exploit Fe-based phenanthroline derivative as a chemotherapeutic agent in cancer treatment.
authors.affiliation: Department of Chemistry, Jinan University , Guangzhou 510632, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Xie
authors.affiliation: Department of Chemistry, Jinan University , Guangzhou 510632, China.
authors.forename: Zuandi
authors.initials: Z
authors.lastname: Luo
authors.affiliation: Department of Chemistry, Jinan University , Guangzhou 510632, China.
authors.forename: Zhennan
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Chemistry, Jinan University , Guangzhou 510632, China.
authors.forename: Tianfeng
authors.identifier: 0000-0001-6953-1342
authors.initials: T
authors.lastname: Chen
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D058085:Iron Compounds / Q000494:pharmacology*; D013880:Thioredoxin-Disulfide Reductase / Q000037:antagonists & inhibitors*
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D058085:Iron Compounds; D013880:Thioredoxin-Disulfide Reductase