Four copper(II) compounds synthesized by anion regulation: Structure, anticancer function and anticancer mechanism.
Copper (Cu) compounds are a promising candidate for next generation metal anticancer drugs. Therefore, we regulated anions to synthesize four mononuclear and binuclear Cu(II) compounds derived from thiosemicarbazone Schiff base ligands and characterized them. Four of these compounds showed very high cytotoxicity to cancer cell lines in vitro. These Cu(II) compounds strongly promoted the apoptosis of BEL-7404 cells and had a capacity to arrest the cell cycle at S phase of those cells. Furthermore, reactive oxygen species (ROS), mitochondrial membrane potential and Western blot analyses revealed that these Cu(II) compounds exert their cytotoxicity through an ROS-mediated intrinsic mitochondrial pathway accompanied by the regulation of Bcl-2 family proteins.
Key Laboratory of Ecology of Rare and Endangered Species and Environmental Protection, Ministry of Education of the People's Republic of China, Guangxi Normal University, Guilin, Guangxi, China.
Zhenlei
Z
Zhang
State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, Ministry of Science and Technology of China, Guangxi Normal University, Guilin, Guangxi, China.
Yi
Y
Gou
State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, Ministry of Science and Technology of China, Guangxi Normal University, Guilin, Guangxi, China.
Jun
J
Wang
State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, Ministry of Science and Technology of China, Guangxi Normal University, Guilin, Guangxi, China.
Kun
K
Yang
State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, Ministry of Science and Technology of China, Guangxi Normal University, Guilin, Guangxi, China.
Jinxu
J
Qi
Guangxi Universities Key Laboratory of Stem Cell and Pharmaceutical Biotechnology, Guangxi Normal University, Guilin, Guangxi, China.
Zuping
Z
Zhou
Key Laboratory of Ecology of Rare and Endangered Species and Environmental Protection, Ministry of Education of the People's Republic of China, Guangxi Normal University, Guilin, Guangxi, China.
Shichu
S
Liang
State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, Ministry of Science and Technology of China, Guangxi Normal University, Guilin, Guangxi, China.
Hong
H
Liang
Key Laboratory of Ecology of Rare and Endangered Species and Environmental Protection, Ministry of Education of the People's Republic of China, Guangxi Normal University, Guilin, Guangxi, China; State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, Ministry of Science and Technology of China, Guangxi Normal University, Guilin, Guangxi, China. Electronic address: fyang@mailbox.gxnu.edu.cn.
Feng
F
Yang
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D003300:Copper / Q000737:chemistry*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008958:Models, Molecular; D008968:Molecular Conformation; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013882:Thiosemicarbazones / Q000737:chemistry
D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D017382:Reactive Oxygen Species; D013882:Thiosemicarbazones; D003300:Copper
Bcl-2 family proteins; Copper compound; Mitochondrial membrane potential; Reactive oxygen species; Thiosemicarbazone Schiff base ligands