Isatin-Schiff base-copper (II) complex induces cell death in p53-positive tumors

靛蓝-席夫碱-铜(II)复合物诱导 p53 阳性肿瘤细胞死亡

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作者:Emil Bulatov, Regina Sayarova, Rimma Mingaleeva, Regina Miftakhova, Marina Gomzikova, Yuri Ignatyev, Alexey Petukhov, Pavel Davidovich, Albert Rizvanov, Nickolai A Barlev

Abstract

Medicinal bioinorganic chemistry is a thriving field of drug research for cancer treatment. Transition metal complexes coordinated to essential biological scaffolds represent a highly promising class of compounds for design of novel target-specific therapeutics. We report here the biological evaluation of a novel Isatin-Schiff base derivative and its Cu(II) complex in several tumor cell lines by assessing their effects on cellular metabolism, real-time cell proliferation and induction of apoptosis. Further, the impact of compounds on the p53 protein and expression of its target genes, including MDM2, p21/CDKN1A, and PUMA was evaluated. Results obtained in this study provide further evidence in support of our prior data suggesting the p53-mediated mechanism of action for Isatin-Schiff base derivatives and their complexes and also shed light on potential use of these compounds for stimulation of apoptosis in breast cancer cells via activation of the pro-apoptotic PUMA gene.

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