Cytotoxicity of a newly synthesized nitroxide derivative of 4-ferrocenecarboxyl-2,2,6,6-tetramethylpiperidine-1-oxyl in high metastatic lung tumor cells.
Low molecular weight nitroxides are widely used as electron paramagnetic resonance (EPR)-detectable spin labels in the biological and pathological areas. A novel nitroxide derivative, 4-ferrocenecarboxyl-2,2,6,6-tetramethyl piperidine-1-oxyl (FC-TEMPO), was synthesized for evaluating the effects of spin label compounds on tumor cells and firstly its biological effects on tumor and normal cells were evaluated. The cytotoxicity of FC-TEMPO in the high metastatic lung carcinoma cells (95-D) showed that it markedly inhibited the viability of cancer cells in a dose-dependent manner, while it was less toxic to a normal human cell line. Further studies found that FC-TEMPO suppressed the growth of tumor cells by induced apoptosis through activating caspase-3 but not caspase-8 which was proved by caspase inhibitors, and the cell cycle arrest at G1 phase. Moreover, the concomitant increase of superoxide dismutase (SOD) and catalase (CAT) activity was observed. Taken together, these results might provide a base for further anticancer investigations of nitroxides and their potential pharmacological applications.
Wu
Y
Y
Center of Analysis and Testresearch, East China University of Science and Technology, Shanghai, PR China.
Tang
W
W
Li
C L
CL
Liu
J W
JW
Miao
L D
LD
Han
J
J
Lan
M B
MB
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005296:Ferrous Compounds / Q000627:therapeutic use*; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D007202:Indicators and Reagents; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D009362:Neoplasm Metastasis / Q000473:pathology; D010880:Piperidines / Q000627:therapeutic use*; D013482:Superoxide Dismutase / Q000378:metabolism
C517890:4-ferrocenecarboxyl-2,2,6,6-tetramethyl piperidine-1-oxyl; D000970:Antineoplastic Agents; D005296:Ferrous Compounds; D007202:Indicators and Reagents; D010880:Piperidines; D007770:L-Lactate Dehydrogenase; D002374:Catalase; D013482:Superoxide Dismutase; D053148:Caspase 3; D053181:Caspase 8