Research Information System
CELL BIOCHEMISTRY AND BIOPHYSICS, no.4, pp.729-746, 2021 (SCI-Expanded)
Herein, we report the synthesis, characterization and anticancer activity of six novel complexes of non-steroidal anti-inflammatory drug niflumic acid with Co(II) and Ni(II). In vitro cytotoxicity screening in MCF-7, HepG2 and HT-29 cancer cell lines showed that the complex 3 [Co(nif)(2)(met)(4-pic)] and complex 6 [Ni(nif)(2)(met)(4-pic)] among all the complexes exhibited the highest cytotoxicity against MCF-7 cells with IC50 values of 11.14 mu M and, 41.47 mu M, respectively. Besides, all the complexes exhibited significantly higher selectivity towards mouse fibroblast 3T3L1 cells. Further mechanistic studies with both complexes on MCF-7 cells revealed their cytotoxic action through the mitochondrial-dependent apoptotic pathway causing an increase oxidative/nitrosative stress, decrease in mitochondrial membrane potential (Delta psi m), inducing the multicaspase activation and arresting the cell cycle at S phase. q-PCR analysis resulted in an increase in the expression of the apoptotic marker proteins bax, p53 and caspase-3 and -8 in MCF-7 cells, but a decrease in the expression of antiapoptotic bcl-2 gene. Moreover, both complexes induced the apoptosis through the inhibition of PI3K/Akt signaling pathway by decreasing the expression of PI3K and increasing dephosphorylation form of Akt protein. These results provide a significant contribution to the explanation of the anticancer mechanisms of these complexes in MCF-7 cells.