Cytotoxic activity, DNA damage, cellular uptake, apoptosis and western blot analysis of ruthenium(II) polypyridyl complex against human lung decarcinoma A549 cell.
A new ruthenium(II) polypyridyl complex [Ru(dmp)2(pddppn)](ClO4)2Ru1 was synthesized and characterized. The cytotoxic activity in vitro of the complex was evaluated by MTT method. Ru1 shows high effect on the inhibition of the cell growth against BEL-7402, HeLa, MG-63 and A549 cells with low IC50 values of 1.6±0.4, 9.0±0.8, 1.5±0.2 and 1.5±0.3 μM, respectively. The cellular uptake indicates that Ru1 can enter into the cytoplasm and accumulate in the cell nuclei. Ru1 can induce apoptosis in A549 cells and enhance the levels of reactive oxygen species (ROS) and induce the decrease of mitochondrial membrane potential. In addition, Ru1 can down-regulate the levels of Bcl-2, Bcl-x, Bak, and Bim expression and up-regulate the expression of Bag-1 and Bad. The complex induces apoptosis of A549 cells through an intrinsic ROS-mediated mitochondrial dysfunction pathway, which was accompanied by regulating the expression of caspases and Bcl-2 family proteins.
School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, PR China.
Shang-Hai
SH
Lai
School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, PR China.
Guang-Bin
GB
Jiang
Instrumentation Analysis and Research Center, Sun Yat-Sen University, Guangzhou 510275, PR China.
Jun-Hua
JH
Yao
School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, PR China.
Wei
W
Li
School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, PR China.
Bing-Jie
BJ
Han
School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, PR China.
Cheng
C
Zhang
School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, PR China.
Chuan-Chuan
CC
Zeng
School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, PR China. Electronic address: lyjche@163.com.
Yun-Jun
YJ
Liu
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D017209:Apoptosis; D001692:Biological Transport; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000494:pharmacology*; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D004249:DNA Damage; D006367:HeLa Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D010618:Phenanthrolines / Q000138:chemical synthesis / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012428:Ruthenium / Q000737:chemistry
D000970:Antineoplastic Agents; D056831:Coordination Complexes; D010618:Phenanthrolines; D017382:Reactive Oxygen Species; D012428:Ruthenium
Apoptosis; Cell cycle arrest; Mitochondrial membrane potential; Ruthenium(II) complex; Western blot analysis