Silver ciprofloxacin (CIPAG): a multitargeted metallodrug in the development of breast cancer therapy

IF 2.7 3区化学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

JBIC Journal of Biological Inorganic Chemistry Pub Date : 2024-04-06 DOI:10.1007/s00775-024-02048-y

Christina N. Banti, Foteini D. Kalousi, Anna-Maria G. Psarra, Eleni E. Moushi, Demetres D. Leonidas, Sotiris K. Hadjikakou

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Abstract

The anti-proliferative activity of the known metalloantibiotic {[Ag(CIPH)₂]NO₃∙0.75MeOH∙1.2H₂O} (CIPAG) (CIPH = ciprofloxacin) against the human breast adenocarcinoma cancer cells MCF-7 (hormone dependent (HD)) and MDA-MB-231 (hormone independent (HI)) is evaluated. The in vitro toxicity and genotoxicity of the metalloantibiotic were estimated toward fetal lung fibroblast (MRC-5) cells. The molecular mechanism of the CIPAG activity against MCF-7 cells was clarified by the (i) cell morphology, (ii) cell cycle arrest, (iii) mitochondrial membrane permeabilization, and (iv) by the assessment of the possible differential effect of CIPAG on estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ) transcriptional activation, applying luciferase reporter gene assay. Moreover, the ex vivo mechanism of CIPAG was clarified by its binding affinity toward calf thymus (CT-DNA).

Graphical abstract

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环丙沙星银（CIPAG）：一种用于开发乳腺癌疗法的多靶点金属药物

摘要评估了已知金属抗生素{[Ag(CIPH)2]NO3∙0.75MeOH∙1.2H2O}（CIPAG）（CIPH = 环丙沙星）对人类乳腺癌细胞 MCF-7（激素依赖型（HD））和 MDA-MB-231（激素独立型（HI））的抗增殖活性。评估了金属抗生素对胎肺成纤维细胞（MRC-5）的体外毒性和遗传毒性。通过(i)细胞形态、(ii)细胞周期停滞、(iii)线粒体膜通透，以及(iv)应用荧光素酶报告基因检测法评估 CIPAG 对雌激素受体 alpha（ERα）和雌激素受体 beta（ERβ）转录激活可能产生的不同影响，阐明了 CIPAG 对 MCF-7 细胞的分子机制。此外，通过CIPAG与小牛胸腺（CT-DNA）的结合亲和力，阐明了CIPAG的体内外作用机制。图表摘要

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来源期刊

JBIC Journal of Biological Inorganic Chemistry 化学-生化与分子生物学

CiteScore

5.90

自引率

3.30%

发文量

审稿时长

3 months

期刊介绍： Biological inorganic chemistry is a growing field of science that embraces the principles of biology and inorganic chemistry and impacts other fields ranging from medicine to the environment. JBIC (Journal of Biological Inorganic Chemistry) seeks to promote this field internationally. The Journal is primarily concerned with advances in understanding the role of metal ions within a biological matrix—be it a protein, DNA/RNA, or a cell, as well as appropriate model studies. Manuscripts describing high-quality original research on the above topics in English are invited for submission to this Journal. The Journal publishes original articles, minireviews, and commentaries on debated issues.