Synergistic interaction between a mixed ligand copper (II) chelate complex and two anticancer agents in T47D human breast cancer cells in vitro.
OBJECTIVE
We have developed a copper(II) chelate complex with a tridentate ONN-Schiff ligand and the anion of salicylate, showing a potent cytotoxic activity against a panel of human and murine cancer cell lines. In this experiment we have explored the combination effect between Cu(SalNEt(2))salicylate (Cu-Sal) complex and two widely used drugs in cancer chemotherapy, bleomycin (BLM) and 5-fluorouracil (5-FU), against T47D human breast cancer cells. Previous theoretical quantum-chemical studies of this complex and ass adducts with biological molecules elucidated the underlying mechanism of action of this complex.


METHODS
Cells grown in adherence in 96-well microplates were exposed simultaneously to both agents for 48 h. During cytotoxicity was assessed via the XTT colorimetric assay. The combined drug interaction was assessed with the median-effect analysis and the combination index (CI).


RESULTS
Concurrent treatment of cells with Cu-Sal complex and the chemotherapeutic drugs BLM and 5-FU and the antioxidant agent ascorbic acid (AsA) resulted mainly in synergistic interaction for most concentration ratios.


CONCLUSIONS
Cu-Sal complex interacts synergistically with the chemotherapeutic drugs for most schedules of administration. These findings call for prompting to search for possible interaction of this complex with other cellular elements of fundamental importance in cell proliferation.
Geromichalos
G D
GD
Laboratory of Cell Culture - Molecular Modeling and Drug Design, Symeonidio Research Center, Theagenio Cancer Hospital, Thessaloniki, Greece. gerom@chem.auth.gr
Trafalis
D T
DT
Katsoulos
G A
GA
Papageorgiou
A
A
Dalezis
P
P
Triandafillidis
E B
EB
Hadjikostas
C C
CC
Athanassiou
A
A
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001761:Bleomycin / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D004347:Drug Interactions; D004357:Drug Synergism; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008024:Ligands; D009942:Organometallic Compounds / Q000494:pharmacology*; D012459:Salicylates / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D008024:Ligands; D009942:Organometallic Compounds; D012459:Salicylates; D001761:Bleomycin; C025564:copper salicylate complex; D005472:Fluorouracil