In vitro and in vivo anticancer activity of nickel (II) tetraazamacrocyclic diperchlorate complex, [(Ni-Me8[14]diene)(ClO4)2] against ehrlich ascites carcinoma (EAC) and MCF7 cells

Cancer remains a global health burden, with a pressing need for more effective treatments. This study uses a novel compound, Nickel (II) diperchlorate complex of the ligand (L): 3,10-C-meso-3,5,7,7,10,12,14,14-octamethyl-1,4,8,11-tetraazacyclotetradeca-4,11-diene, Me₈[14]diene, designated as [Ni(II)L](ClO₄)₂, to explore its potential as an anticancer agent. Its efficacy was evaluated against Ehrlich Ascites Carcinoma (EAC)-bearing Swiss albino mice by monitoring tumor cell growth inhibition, survival time, tumor mass reduction, and hematological profiles. Additionally, cytotoxicity was investigated in vitro using MCF7 breast cancer cells. The apoptotic potential was evaluated through Hoechst staining, with changes in apoptosis-related gene expression (p53, BCL2, BAX, PARP1, CASP3, CASP8, and CASP9) using RT-qPCR. The test compound's toxicity was evaluated by monitoring hematological, biochemical, and histological changes. The compound exhibited dose-dependent growth inhibition of EAC cells with 88.45% inhibition at a dose of 200 µg/kg (p < 0.01), extended lifespan by 52.63%, reduced tumor weight by 47.83%, and restored hematological parameters in EAC-bearing mice. Cytotoxicity assays yielded LC₅₀ and IC₅₀ values of 23.73 µg/mL and 71.52 µg/mL, respectively. Apoptosis induction was evidenced by cell membrane blebbing, apoptotic body formation, chromosomal condensation, and nuclear fragmentation in MCF7 cells. Significant upregulation of pro-apoptotic genes such as p53, BAX, PARP1, CASP3, CASP8, and CASP9, alongside downregulation of anti-apoptotic gene BCL2, implied activation of the apoptotic pathway in cancer cells, followed by compound treatment. Moreover, no long-term negative impacts on tissue levels or hematological or biochemical markers were noted in the mice. Altogether, [Ni(II)L](ClO₄)₂ demonstrates promising anticancer activity and could serve as a potential chemotherapeutic agent, pending further studies.