Effect of Schiff base Cu(II) complexes on signaling pathways in HT-29 cells.
Mol Med Rep
; 14(5): 4436-4444, 2016 Nov.
Article
in En
| MEDLINE
| ID: mdl-27633628
ABSTRACT
Schiff base copper (II) complexes are known for their anticancer, antifungal, antiviral and antiinflammatory activities. The aim of the current study was to investigate biological effects of Schiff base Cu (II) complexes (0.001100 µmol/l)[Cu2(salD, Lglu)2(isoquinoline)2]·2C2H5OH (1), [Cu(sal5metLglu)(H2O)].H2O (2), [Cu(ethanol)2(imidazole)4][Cu2(salD, L-glu)2(imidazole)2] (3), [Cu(salD,Lglu)(2methylimidazole)] (4) on the human colon carcinoma cells HT29, the mouse noncancerous cell line NIH3T3 and the human noncancerous fibroblast cell line VH10. The results suggested that Cu (II) complexes exhibit cytotoxic effects against the HT29 cell line, while complexes 3 and 4 were the most effective. Subsequent to 72 h of incubation, apoptosis was observed in the HT29 cells induced by Cu (II) complexes 1 (0.1, 1, 10 and 50 µmol/l), 2 (1, 10, 50 and 100 µmol/l), 3 (0.01, 1, 10 and 50 µmol/l) and 4 (0.01, 0.1, 1 and 10 µmol/l). The apoptotic pathways activated by the Cu (II) complexes were identified. The results indicated that complexes 2, 3 and 4 were able to induce the mitochondriadependent pathway of apoptosis in HT29 cells, while complex 1 was obsered to activate the extrinsic pathway of apoptosis. The levels of the antiapoptotic protein Bcl2 were reduced and those of the proapoptotic protein Bax increased following treatment with complexes 2, 3 and 4. Complex 1 had no effect on Bax protein expression. Complexes 2 and 3 induced elevation of cytochrome c (cyt c), while complex 4 induced a timedependent elevation of cyt c levels. No cyt c was detected in HT29 cells exposed to complex 1, suggesting that Cu (II) complexes activated the extrinsic pathway of apoptosis. The results from the current study in addition to previous studies suggest that Schiff base Cu (II) complexes have potential as novel anticancer drugs.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Schiff Bases
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Colonic Neoplasms
/
Copper
/
Mitochondria
Limits:
Animals
/
Humans
Language:
En
Journal:
Mol Med Rep
Year:
2016
Document type:
Article
Publication country:
GR
/
GRECIA
/
GREECE
/
GRÉCIA