| After the accidental discovery of cis-platinum, extensive attempts have centralized on the rational
design of metallic compounds for cancer treatment. Here a solvent-dependent complex of nickel (II)
with 1,10-phenanthroline and naproxen, [Ni(1,10-phenanthroline)(naproxen)2(solvent)], solvent ¼ 83%
H2O and 17% EtOH in the crystal structure, has been synthesized and specified by the X-ray structure
analysis. It’s in vitro DNA binding was inspected by the multispectroscopic methods and gel electrophoresis.
The data of DNA-viscosity and competition fluorimetric test by methylene blue (MB) and
Hoechst 33258 confirm groove binding mode of the complex to CT-DNA. Comparison of the results of
this binding study with previous work revealed that the mode of binding of small compounds to DNA
is highly influenced by the structure of the compounds. The DNA cleavage potency of the complex
was appraised by the agarose gel electrophoretic and it was found that the complex does not have
any momentous cleavage potency on the pUC18 plasmid DNA. The cytotoxicity of the complex on HT
29, HepG2 and HEK-293 cell lines by MTT method indicates that %inhibition of the complex on HT 29
is better than HepG2, compared with cisplatin drug. On HEK-293 cells, %inhibition growth of normal
cells of the complex is less than cisplatin. Flow cytometry analysis of the complex on the HT 29 cells
indicated the apoptosis cell death. RT-PCR studies revealed down-regulation of BCL2 expression, while
the expression of BAX, caspase 3 and BAX/BCL2 genes was up-regulated in HT 29 cells by the complex. |