Anticancer activity of two novel ruthenium compounds in gastric cancer cells.

AIMS: Ruthenium (II) complexes are promising anticancer molecules due its pharmacological properties and selectivity to cells tumor. The aim of this work was to study the cytotoxic activity, and apoptosis induction of two new ruthenium complexes on a human gastric cancer cell line. MAIN METHODS: Two ruthenium(II) complexes were synthesized: [(H2pbbzim)Ru(tpy-Ph-COOCH3)](Cl)2 (Ru-UCN1), and [(tpy)Ru(tpy-Ph-bzH)](Cl)2 (Ru-UCN3), and their anticancer capacity determined by cytotoxic assays, gene expression analysis, caspase activation and confocal microscopy. KEY FINDINGS: Ru-UCN3 is more notably cytotoxic than cisplatin in human gastric cancer cells AGS at 24 h, while Ru-UCN1 is more active against gastric cancer cells than cisplatin at 48 h. The complexes induce apoptosis as shown by RT-qPCR, protease activity, and confocal microscopy. Ru-UCN1 induces the overexpression of pro-apoptotic genes at 3 and 6 h, whereas Ru-UCN3 induces overexpression of these genes at 12 and 24 h. Ru-UCN1 treatment shows a strong activation of caspases 3/7 at 24 h, which was not observed for Ru-UCN3 treatment in the same timeframe. SIGNIFICANCE: Taken together, this data suggests that Ru-UCN1 and to a lesser extent, Ru-UCN3, may be interesting anticancer agents for gastric cancer.

Reexamining the Mössbauer effect as a means to cleave DNA.

The ability of a DNA-bound Mössbauer isotope to absorb resonant gamma-radiation and subsequently, upon decay, induce DNA double-strand breaks by emission of low-energy Auger electrons was examined with a simple plasmid DNA cleavage assay. This mechanism was postulated by Mills et al. [Mills et al. (1988) Nature 336, 787] in the observed ablation of tumor cell growth with 57Fe(III)-bleomycin and Mössbauer radiation. The observed linearization of supercoiled pAA15 plasmid DNA upon treatment with five or more 57Fe(III)-bleomycin per plasmid precluded its use for testing Mössbauer effect induced cleavage. An alternative 57Fe-DNA-binding complex, [57Fe(phen)2(DPPZ)](PF6)2.H2O (57(1)), was synthesized and found to tightly bind DNA (K = 9.8 x 10(5) M-1) yet not induce DNA nicks or cuts at loadings of less than 500/pAA15 plasmid. Mössbauer irradiation of 57(1)/pAA15 samples under frozen and solution conditions does not result in observable linearization of the plasmid DNA over control samples. Some linearization is observed in all irradiated samples but is attributed only to the photoelectric effect.