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Mechanistic studies in MCF-7 include cell morphology, cell-cycle arrest, mitochondrial membrane permeabilization, and estrogen receptor alpha/beta transcriptional activation via luciferase reporter assays, while ex vivo binding affinity to calf thymus DNA is assessed.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/silver-ciprofloxacin-cipag-a-multitargeted-metallodrug-in-the-development-of-breast-cancer-therapy/336274/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/silver-ciprofloxacin-cipag-a-multitargeted-metallodrug-in-the-development-of-breast-cancer-therapy/336274.png","ImageObject",300,407,{"name":92,"@type":93},"Eliana","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-27","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":52},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is CIPAG and what cancer models were tested?","Question",{"text":112,"@type":113},"CIPAG is a silver(I)-ciprofloxacin metalloantibiotic. Its anti-proliferative activity was evaluated against MCF-7 and MDA-MB-231 breast adenocarcinoma cells.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How was CIPAG activity investigated at the molecular level in MCF-7 cells?",{"text":117,"@type":113},"The study examined cell morphology, cell-cycle arrest, mitochondrial membrane permeabilization, and effects on ERα and ERβ transcriptional activation using a luciferase reporter gene assay.",{"name":119,"@type":110,"acceptedAnswer":120},"What ex vivo or toxicity/genotoxicity evaluations were performed?",{"text":121,"@type":113},"In vitro toxicity and genotoxicity were tested in MRC-5 fetal lung fibroblast cells, and the ex vivo mechanism included assessing CIPAG binding affinity toward calf thymus DNA.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},336274,1790438248,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":52,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":52,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144},4398048949847,"https://ap-avatar.wpscdn.com/avatar/400002536579ef2da7f?_k=1778318612642679267","JBIC Journal of Biological Inorganic Chemistry (2024) 29:177–186  \n[https://doi.org/10.1007/s00775-024-02048-y](https://doi.org/10.1007/s00775-024-02048-y)  \nSilver ciprofloxacin (CIPAG): a multitargeted metallodrug in the development of breast cancer therapy  \nChristina N. Banti1 · Foteini D. Kalousi2 · Anna‑Maria G. Psarra2 · Eleni E. Moushi3 · Demetres D. Leonidas2 ·  \nSotiris K. Hadjikakou1,4  \nReceived: 24 December 2023 / Accepted: 6 March 2024 / Published online: 6 April 2024 © The Author(s) 2024  \nAbstract  \nThe 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) .  \nGraphical abstract  \nKeywords Biological inorganic chemistry · Silver(I) compounds · Ciprofloxacin · Metalloantibiotics · Antitumor activity · Molecular mechanism  \nIntroduction  \nChemotherapy stands out as among the most effective treatments for cancer. Antitumor antibiotics like doxorubicin  \nExtended author information available on the last page of the article or daunomycin are widely recognized among clinically  \nchemotherapeutics in use [1] . Nowadays, antibiotics have found application as anticancer medications, notably in cases of cancers related to bacteria, such as gastric and cervical cancers [1]. Thus, antibiotics not only serve as drugs against bacterial infections but also exhibit effectiveness in impeding the growth of cancer cells [2] .  \nCiprofloxacin, a fluoroquinolone, is widely utilized as abroad-spectrum antibiotic known for its minimal side effects [3] . Fluoroquinolones, a class of antibiotics, function by inhibiting both bacterial DNA gyrase and a type II topoisomerase called topoisomerase IV [1] . Furthermore, apart from possessing antitumor characteristics, fluoroquinolones exhibit diversified biological profiles, showcasing properties that extend to being anti-tubercular, anti-HIV, anti-malarial, anti-Alzheimer, etc. [4] . Especially, ciprofloxacin induces time-and dose-dependent growth inhibition and apoptosis of a plethora of cancer cells, such as prostate, colorectal, leukemia, and breast cell lines [1, 3] . The suggested apoptotic mechanism of ciprofloxacin involves the disruption of mitochondrial membrane potential, followed by a secondary activation of caspase-8 [1]. Moreover, it inhibits cell proliferation by causing damage to mitochondrial DNA and interacts with the mitochondrial topoisomerase II isoform [5] .  \nIn the course of our studies for the development of new efficient targeted chemotherapeutics [6–12], the in vitro antiproliferative activity of the conjugate of silver(I) with ciprofloxacin {[Ag(CIPH)2]NO3∙0.75MeOH∙1.2H2O} (CIPAG)(CIPH = ciprofloxacin) (Chart 1) against MCF-7 (HD) and MDA-MB-231 (HI) cells, was screened. In vitro assessments were conducted to evaluate the toxicity and genotoxicity on MRC-5 cells. A range of tests was employed to elucidate the molecular mechanism of CIPAG against MCF-7 cells, both in vitro and ex vivo. Moreover, CIPAG demonstrates significantly greater antimicrobial efficacy (up to 148 times) against bacterial strains P. aeruginosa, S. epidermidis, and S. aureus compared to the commercially accessible hydrochloride salt of ciprofloxacin [6]. The in vivo toxicity of CIPAG wa","cbCaigD1VLnsti3v","https://ap.wps.com/l/cbCaigD1VLnsti3v","pdf",1299996,"English","# Abstract\n# Introduction\n# Results and discussion\n## General aspects","[{\"question\":\"What is CIPAG and what cancer models were tested?\",\"answer\":\"CIPAG is a silver(I)-ciprofloxacin metalloantibiotic. Its anti-proliferative activity was evaluated against MCF-7 and MDA-MB-231 breast adenocarcinoma cells.\"},{\"question\":\"How was CIPAG activity investigated at the molecular level in MCF-7 cells?\",\"answer\":\"The study examined cell morphology, cell-cycle arrest, mitochondrial membrane permeabilization, and effects on ERα and ERβ transcriptional activation using a luciferase reporter gene assay.\"},{\"question\":\"What ex vivo or toxicity/genotoxicity evaluations were performed?\",\"answer\":\"In vitro toxicity and genotoxicity were tested in MRC-5 fetal lung fibroblast cells, and the ex vivo mechanism included assessing CIPAG binding affinity toward calf thymus DNA.\"}]","Silver ciprofloxacin (CIPAG) - a multitargeted metallodrug in the development of breast cancer therapy | PDF",1790014344,25]