Silver ciprofloxacin (CIPAG): a multitargeted metallodrug in the development of breast cancer therapy
Tóm tắt
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).
Từ khóa
Tài liệu tham khảo
Zheng Y, Kng J, Yang C, Hedrickc JL, Yan Yang Y (2021) Cationic polymer synergizing with chemotherapeutics and re-purposing antibiotics against cancer cells. Biomater Sci 9:2174–2182
Kassab AE, Gedawy EM (2018) Novel ciprofloxacin hybrids using biology oriented drug synthesis (BIODS) approach: anticancer activity, effects on cell cycle profile, caspase-3 mediated apoptosis, topoisomerase II inhibition, and antibacterial activity. Eur J Med Chem 150:403–418
Herold C, Ocker M, Ganslmayer M, Gerauer H, Hahn EG, Schuppan D (2002) Ciprofloxacin induces apoptosis and inhibits proliferation of human colorectal carcinoma cells. Br J Cancer 86:443–448
Ezelarab HAA, Abbas SH, Hassan HA, Abuo-Rahma G-DA (2018) Recent updates of fluoroquinolones as antibacterial agents. Arch Pharm Chem Life Sci 351:1800141
Chrzanowska A, Roszkowski P, Bielenica A, Olejarz W, Stepien K, Struga M (2020) Anticancer and antimicrobial effects of novel ciprofloxacin fatty acids conjugates. Eur J Med Chem 185:111810
Milionis I, Banti CN, Sainis I, Raptopoulou CP, Psycharis V, Kourkoumelis N, Hadjikakou SK (2018) Silver ciprofloxacin (CIPAG): a successful combination of antibiotics in inorganic-organic hybrid for the development of novel formulations based on chemically modified commercially available antibiotics. J Biol Inorg Chem 23:705–723
Banti CN, Papatriantafyllopoulou C, Papachristodoulou C, Hatzidimitriou AG, Hadjikakou SK (2023) New apoptosis inducers containing anti-inflammatory drugs and pnictogen derivatives: a new strategy in the development of mitochondrial targeting chemotherapeutics. J Med Chem 66(6):4131–4149
Banti CN, Papatriantafyllopoulou C, Manoli M, Tasiopoulos AJ, Hadjikakou SK (2016) Nimesulide silver metallodrugs, containing the mitochondriotropic, triaryl derivatives of pnictogen; anticancer activity against human breast cancer cells. Inorg Chem 55:8681–8696
Banti CN, Giannoulis AD, Kourkoumelis N, Owczarzak A, Kubicki M, Hadjikakou SK (2014) Novel metallo-therapeutics of the NSAID naproxen. Interaction with intracellular components that leads the cells to apoptosis. Dalton Trans 43:6848–6863
Banti CN, Giannoulis AD, Kourkoumelis N, Owczarzak AM, Poyraz M, Kubicki M, Charalabopoulos K, Hadjikakou SK (2012) Mixed ligand–silver(I) complexes with anti-inflammatory agents which can bind to lipoxygenase and calf-thymus DNA, modulating their function and inducing apoptosis. Metallomics 4:545–560
Ozturk II, Hadjikakou SK, Hadjiliadis N, Kourkoumelis N, Kubicki M, Tasiopoulos AJ, Scleiman H, Barsan MM, Butler IS, Balzarini J (2009) New antimony(III) bromide complexes with thioamides: synthesis, characterization, and cytostatic properties. Inorg Chem 48:2233–2245
Kouroulis KN, Hadjikakou SK, Hadjiliadis N, Kourkoumelis N, Kubicki M, Male L, Hursthouse M, Skoulika S, Metsios AK, Tyurin VY, Dolganov AV, Milaeva ER (2009) Synthesis, structural characterization and in vitro cytotoxicity of new Au(III) and Au(I) complexes with thioamides. Oxidation and desulfuration of thioamides by Au(III) ions. Dalton Trans 47:10446–10456
Chrysouli MP, Banti CN, Kourkoumelis N, Moushi EE, Tasiopoulos AJ, Douvalis A, Papachristodoulou C, Hatzidimitriou AG, Bakas T, Hadjikakou SK (2020) Ciprofloxacin conjugated to diphenyltin(IV): a novel formulation with enhanced antimicrobial activity. Dalton Trans 49:11522
Wallis SC, Gahan LR, Charles BG, Hambley TW, Duckworth PA (1996) Copper(II) complexes of the fluoroquinolone antimicrobial ciprofloxacin. Synthesis, X-ray structural characterization, and potentiometric study. J Inorg Biochem 62:1–16
Farrokhpour H, Hadadzadeh H, Darabi F, Abyar F, Rudbari HA, Ahmadi-Bagheria T (2014) A rare dihydroxo copper(II) complex with ciprofloxacin; a combined experimental and ONIOM computational study of the interaction of the complex with DNA and BSA. RSC Adv 4:35390–35404
Khalil TE, El-Dissouky A, Al-Wahaib D, Abrar NM, El-Sayed DS (2020) Synthesis, characterization, antimicrobial activity, 3DQSAR, DFT, and molecular docking of some ciprofloxacin derivatives and their copper(II) complexes. Appl Organomet Chem 34:e5998
Ptaszynska N, Gucwa K, Olkiewicz K, Heldt M, Serocki M, Stupak A, Martynow D, Debowski D, Gitlin-Domagalska A, Lica J, Łegowska A, Milewski S, Rolka K (2020) Conjugates of ciprofloxacin and levofloxacin with cell-penetrating peptide exhibit antifungal activity and mammalian cytotoxicity. Int J Mol Sci 21:4696
Farghadani R, Rajarajeswaran J, Hashim NBM, Abdulla MA, Muniandy S (2017) A novel β-diiminato manganese III complex as the promising anticancer agent induces G0/G1 cell cycle arrest and triggers apoptosis via mitochondrial-dependent pathways in MCF-7 and MDA-MB-231 human breast cancer cells. RSC Adv 7:24387–24398
Hollville E, Martin SJ (2016) Measuring apoptosis by microscopy and flow cytometry. Curr Protoc Immunol 112:14381–143824
Khamchun S, Thongboonkerd V (2018) Cell cycle shift from G0/G1 to S and G2/M phases is responsible for increased adhesion of calcium oxalate crystals on repairing renal tubular cells at injured site. Cell Death Discov 4:106
Qin J-L, Shen W-Y, Chen Z-F, Zhao L-F, Qin Q-P, Yu Y-C, Liang H (2017) Oxoaporphine metal complexes (CoII, NiII, ZnII) with high antitumor activity by inducing mitochondria-mediated apoptosis and S-phase arrest in HepG2. Sci Rep 7:46056
Kraichely DM, Sun J, Katzenellenbogen JA, Katzenellenbogen BS (2000) Conformational changes and coactivator recruitment by novel ligands for estrogen receptor-alpha and estrogen receptor-beta: correlations with biological character and distinct differences among SRC coactivator family members. Endocrinology 141:3534–3545
Gorgogietas VA, Tsialtas I, Sotiriou N, Laschou VC, Karra AG, Leonidas DD, Chrousos GP, Protopapa E, Psarra AG (2018) Potential interference of aluminum chlorohydrate with estrogen receptor signaling in breast cancer cells. J Mol Biochem 7:1–13
Weatherman RV, Clegg NJ, Scanlan TS (2001) Differential SERM activation of the estrogen receptors (ERalpha and ERbeta) at AP-1 sites. Chem Biol 8:427–436
Fotouhi L, Atoofi Z, Heravi MM (2013) Interaction of ciprofloxac in with DNA studied by spectroscopy and voltammetry at MWCNT/DNA modified glassy carbon electrode. Talanta 103:194–200
Kellett A, Molphy Z, Slator C, McKee V, Farrell NP (2019) Molecular methods for assessment of non-covalent metallodrug–DNA interactions. Chem Soc Rev 48:971
Chouai A, Wicke SE, Turro C, Bacsa J, Dunbar KR, Wang D, Thumme RP (2005) Ruthenium(II) complexes of 1,12-diazaperylene and their interactions with DNA. Inorg Chem 44:5996–6003
Sirajuddin M, Ali S, Badshah A (2013) Drug–DNA interactions and their study by UV–Visible, fluorescence spectroscopies and cyclic voltammetry. J Photochem Photobiol B 124:1–19
Aazam ES, Zaki M (2020) Synthesis and characterization of Ni(II)/Zn(II) metal complexes derived from Schiff base and ortho-phenylenediamine: in vitro DNA binding, molecular modeling and RBC hemolysis. ChemistrySelect 5:610–618
Luo H, Liang Y, Zhang H, Liu Y, Xiao Q, Huang S (2021) Comparison on binding interactions of quercetin and its metal complexes with calf thymus DNA by spectroscopic techniques and viscosity measurement. J Mol Recognit 34:293
Banti CN, Piperoudi AA, Raptopoulou CP, Psycharis V, Athanassopoulos CM, Hadjikakou SK (2024) Mitochondriotropic agents conjugated with NSAIDs through metal ions against breast cancer cells. J Inorg Biochem 250:112420
Tsialtas I, Georgantopoulos A, Karipidou ME, Kalousi FD, Karra AG, Leonidas DD, Psarra AG (2021) Anti-apoptotic and antioxidant activities of the mitochondrial estrogen receptor beta in N2A neuroblastoma cells. Int J Mol Sci 22:7620
Georgantopoulos A, Vougioukas A, Kalousi FD, Tsialtas I, Psarra AG (2023) Comparative studies on the anti-inflammatory and apoptotic activities of four Greek essential oils: involvement in the regulation of NF-κΒ and steroid receptor signaling. Life (Basel) 13:1534