Evaluation of central-metal effect on anticancer activity and mechanism ofaction of isostructural Cu(II) and Ni(II) complexes containing pyridine-۲,۶-dicarboxylate

Two Cu(II) (C۱) and Ni(II) (C۲) complexes were designed through the one-pot reaction ofpyridine-۲,۶-dicarboxylic acid and ۲-aminobenzimidazole respectively with copper(II) nitratehexahydrate and nickel(II) nitrate hexahydrate. Both complexes were characterized by singlecrystalX-ray diffraction and the distorted octahedral geometry was recognized for them. TheMTT assay indicated that the complexes have a significant antiproliferative effect on BEL-۷۴۰۴cells. IC۵۰ values confirmed that C۱ (IC۵۰= ۰.۵۶ μM) is several times more potent than C۲ (IC۵۰=۵.۱۳ μM). The similar cellular uptake of the complexes in mentioned cells led to this proposalthat the production of ROS with different values can be the main reason for different cytotoxicityof the complexes. In this study, C۱ and C۲ caused BEL-۷۴۰۴ cells arrest at the G۲/M and Sphases, respectively. The expression of p۵۳, Bax up-regulation, and Bcl-۲ down-regulation andalso activation of procaspase-۹, and ۳ indicated that apoptosis through a caspase-dependentmitochondrion pathway is a remarkable pathway in BEL-۷۴۰۴ cells treated by C۱ whilemechanistic studies proved that C۲ induce death of BEL-۷۴۰۴ cells through the activation ofRAGE/PI۳KC۳/Beclin ۱ autophagic cell signaling pathway, more specifically. The cytostaticeffect of the complexes in the BEL-۷۴۰۴ ۳D spheroid model was depicted

کلیدواژه ها:

Cu(II) and Ni(II) complexes ، Anticancer effect ، Production of ROS ، Apoptosis ، Autophagy.