{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T15:44:54Z","timestamp":1777650294929,"version":"3.51.4"},"reference-count":51,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,4,24]],"date-time":"2023-04-24T00:00:00Z","timestamp":1682294400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007076","name":"Associazione Italiana per la Ricerca sul Cancro (AIRC)","doi-asserted-by":"publisher","award":["IG #13575"],"award-info":[{"award-number":["IG #13575"]}],"id":[{"id":"10.13039\/501100007076","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007076","name":"Associazione Italiana per la Ricerca sul Cancro (AIRC)","doi-asserted-by":"publisher","award":["GA #633937"],"award-info":[{"award-number":["GA #633937"]}],"id":[{"id":"10.13039\/501100007076","id-type":"DOI","asserted-by":"publisher"}]},{"name":"FAR (University Fund for Scientific Research)","award":["IG #13575"],"award-info":[{"award-number":["IG #13575"]}]},{"name":"FAR (University Fund for Scientific Research)","award":["GA #633937"],"award-info":[{"award-number":["GA #633937"]}]},{"name":"European Union","award":["IG #13575"],"award-info":[{"award-number":["IG #13575"]}]},{"name":"European Union","award":["GA #633937"],"award-info":[{"award-number":["GA #633937"]}]},{"name":"Interuniversity Consortium for the Biotechnology","award":["IG #13575"],"award-info":[{"award-number":["IG #13575"]}]},{"name":"Interuniversity Consortium for the Biotechnology","award":["GA #633937"],"award-info":[{"award-number":["GA #633937"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Combined treatments employing lower concentrations of different drugs are used and studied to develop new and more effective anticancer therapeutic approaches. The combination therapy could be of great interest in the controlling of cancer. Regarding this, our research group has recently shown that peptide nucleic acids (PNAs) that target miR-221 are very effective and functional in inducing apoptosis of many tumor cells, including glioblastoma and colon cancer cells. Moreover, in a recent paper, we described a series of new palladium allyl complexes showing a strong antiproliferative activity on different tumor cell lines. The present study was aimed to analyze and validate the biological effects of the most active compounds tested, in combination with antagomiRNA molecules targeting two miRNAs, miR-221-3p and miR-222-3p. The obtained results show that a \u201ccombination therapy\u201d, produced by combining the antagomiRNAs targeting miR-221-3p, miR-222-3p and the palladium allyl complex 4d, is very effective in inducing apoptosis, supporting the concept that the combination treatment of cancer cells with antagomiRNAs targeting a specific upregulated oncomiRNAs (in this study miR-221-3p and miR-222-3p) and metal-based compounds represents a promising therapeutic strategy to increase the efficacy of the antitumor protocol, reducing side effects at the same time.<\/jats:p>","DOI":"10.3390\/pharmaceutics15051332","type":"journal-article","created":{"date-parts":[[2023,4,25]],"date-time":"2023-04-25T01:37:01Z","timestamp":1682386621000},"page":"1332","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Combined Treatment of Cancer Cells Using Allyl Palladium Complexes Bearing Purine-Based NHC Ligands and Molecules Targeting MicroRNAs miR-221-3p and miR-222-3p: Synergistic Effects on Apoptosis"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2340-0552","authenticated-orcid":false,"given":"Chiara","family":"Tupini","sequence":"first","affiliation":[{"name":"Department of Life Sciences and Biotechnology, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6131-3727","authenticated-orcid":false,"given":"Matteo","family":"Zurlo","sequence":"additional","affiliation":[{"name":"Department of Life Sciences and Biotechnology, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Gasparello","sequence":"additional","affiliation":[{"name":"Department of Life Sciences and Biotechnology, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irene","family":"Lodi","sequence":"additional","affiliation":[{"name":"Department of Life Sciences and Biotechnology, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7638-515X","authenticated-orcid":false,"given":"Alessia","family":"Finotti","sequence":"additional","affiliation":[{"name":"Department of Life Sciences and Biotechnology, University of Ferrara, 44121 Ferrara, Italy"},{"name":"Center of Innovative Therapies for Cystic Fibrosis (InnThera4CF), University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Scattolin","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Chimiche, Universit\u00e0 degli Studi di Padova, 35131 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabiano","family":"Visentin","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Molecolari e Nanosistemi, University Ca\u2019 Foscari, 30174 Venezia-Mestre, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberto","family":"Gambari","sequence":"additional","affiliation":[{"name":"Department of Life Sciences and Biotechnology, University of Ferrara, 44121 Ferrara, Italy"},{"name":"Center of Innovative Therapies for Cystic Fibrosis (InnThera4CF), University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1972-7766","authenticated-orcid":false,"given":"Ilaria","family":"Lampronti","sequence":"additional","affiliation":[{"name":"Department of Life Sciences and Biotechnology, University of Ferrara, 44121 Ferrara, Italy"},{"name":"Center of Innovative Therapies for Cystic Fibrosis (InnThera4CF), 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therapy","volume":"2","author":"Bozic","year":"2013","journal-title":"eLife"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1007\/s13346-020-00779-4","article-title":"Simultaneous delivery of anti-miRNA and docetaxel with supramolecular self-assembled \u201cchitosome\u201d for improving chemosensitivity of triple negative breast cancer cells","volume":"11","author":"Sun","year":"2021","journal-title":"Drug Deliv. Trans. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1678","DOI":"10.1016\/j.cell.2017.11.009","article-title":"Combination Cancer Therapy Can Confer Benefit via Patient-to-Patient Variability without Drug Additivity or Synergy","volume":"171","author":"Palmer","year":"2017","journal-title":"Cell"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1089\/nat.2019.0825","article-title":"High Levels of Apoptosis Are Induced in the Human Colon Cancer HT29 Cell Line by Co-Administration of Sulforaphane and a Peptide Nucleic Acid Targeting miR-15b-5p","volume":"30","author":"Gasparello","year":"2020","journal-title":"Nucleic Acid Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"61","DOI":"10.3892\/ijo.2021.5241","article-title":"Synergistic effects of the combined treatment of U251 and T98G glioblastoma cells with an anti-tubulin tetrahydrothieno[2,3-c]pyridine derivative and a peptide nucleic acid targeting miR-221-3p","volume":"59","author":"Zurlo","year":"2021","journal-title":"Int. J. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Zurlo, M., Romagnoli, R., Oliva, P., Gasparello, J., Finotti, A., and Gambari, R. (2022). Synergistic Effects of A Combined Treatment of Glioblastoma U251 Cells with An Anti-miR-10b-5p Molecule and An AntiCancer Agent Based on 1-(3\u2032,4\u2032,5\u2032-Trimethoxyphenyl)-2-Aryl-1H-Imidazole Scaffold. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23115991"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Gasparello, J., Papi, C., Zurlo, M., Gambari, L., Rozzi, A., Manicardi, A., Corradini, R., Gambari, R., and Finotti, A. (2022). Treatment of Human Glioblastoma U251 Cells with Sulforaphane and a Peptide Nucleic Acid (PNA) Targeting miR-15b-5p: Synergistic Effects on Induction of Apoptosis. Molecules, 27.","DOI":"10.3390\/molecules27041299"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.cell.2005.06.030","article-title":"Silence from within: Endogenous siRNAs and miRNAs","volume":"122","author":"Sontheimer","year":"2005","journal-title":"Cell"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4653","DOI":"10.1242\/dev.02073","article-title":"MicroRNA functions in animal development and human disease","volume":"132","author":"Miska","year":"2005","journal-title":"Development"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1038\/nrg1379","article-title":"MicroRNAs: Small RNAs with a big role in gene regulation","volume":"5","author":"He","year":"2004","journal-title":"Nat. Rev. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1517\/14712598.7.7.1009","article-title":"Regulatory mechanisms of microRNAs involvement in cancer","volume":"7","author":"Fabbri","year":"2007","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/2052-8426-2-30","article-title":"Therapeutic Opportunities for Targeting microRNAs in Cancer","volume":"2","author":"Taylor","year":"2014","journal-title":"Mol. Cell. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5","DOI":"10.3892\/ijo.2016.3503","article-title":"Targeting oncomiRNAs and mimicking tumor suppressor miRNAs: \u039dew trends in the development of miRNA therapeutic strategies in oncology (Review)","volume":"49","author":"Gambari","year":"2016","journal-title":"Int. J. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"488","DOI":"10.3389\/fphar.2019.00488","article-title":"Enhanced Inhibition of Tumorigenesis Using Combinations of miRNA-Targeted Therapeutics","volume":"10","author":"Miroshnichenko","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Gajda, E., Godlewska, M., Mariak, Z., Nazaruk, E., and Gawel, D. (2020). Combinatory Treatment with miR-7-5p and Drug-Loaded Cubosomes Effectively Impairs Cancer Cells. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21145039"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"22581","DOI":"10.1002\/jcp.28823","article-title":"The effect of combined miR-200c replacement and cisplatin on apoptosis induction and inhibition of gastric cancer cell line migration","volume":"234","author":"Ghasabi","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1007\/s11060-019-03256-2","article-title":"Clinical impact of circulating oncogenic MiRNA-221 and MiRNA-222 in glioblastoma multiform","volume":"144","author":"Swellam","year":"2019","journal-title":"J. Neurooncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1093\/ajcp\/aqy008","article-title":"Upregulation of miR-125b, miR-181d, and miR-221 Predicts Poor Prognosis in MGMT Promoter-Unmethylated Glioblastoma Patients","volume":"149","author":"Chen","year":"2018","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1007\/s11060-016-2308-5","article-title":"Exosomal miR-221 targets DNM3 to induce tumor progression and temozolomide resistance in glioblastoma","volume":"131","author":"Yang","year":"2017","journal-title":"J. Neurooncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1111\/neup.12129","article-title":"MicroRNA-221 targeting PI3-K\/Akt signaling axis induces cell proliferation and BCNU resistance in human glioblastoma","volume":"34","author":"Xie","year":"2014","journal-title":"Neuropathology"},{"key":"ref_23","first-page":"1621","article-title":"Overexpression of miR-221 and miR-222 in the cancer stroma is associated with malignant potential in colorectal cancer","volume":"40","author":"Iida","year":"2018","journal-title":"Oncol. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"22272","DOI":"10.1002\/jcp.28794","article-title":"Silencing microRNA-221\/222 cluster suppresses glioblastoma angiogenesis by suppressor of cytokine signaling-3-dependent JAK\/STAT pathway","volume":"234","author":"Xu","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.febslet.2013.11.014","article-title":"MicroRNA-221 promotes colorectal cancer cell invasion and metastasis by targeting RECK","volume":"588","author":"Qin","year":"2014","journal-title":"FEBS Lett."},{"key":"ref_26","first-page":"6491","article-title":"miR-221-3p and miR-15b-5p promote cell proliferation and invasion by targeting Axin2 in liver cancer","volume":"18","author":"Dong","year":"2019","journal-title":"Oncol. Lett."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1080\/21691401.2017.1315429","article-title":"MicroRNA-221-3p is up-regulated and serves as a potential biomarker in pancreatic cancer","volume":"46","author":"Li","year":"2018","journal-title":"Artif. Cells Nanomed. Biotechnol."},{"key":"ref_28","first-page":"604","article-title":"miR-221-3p promotes the cell growth of non-small cell lung cancer by targeting p27","volume":"20","author":"Yin","year":"2019","journal-title":"Mol. Med. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"13616","DOI":"10.1039\/C8DT01831F","article-title":"Synthesis of new allyl palladium complexes bearing purine-based NHC ligands with antiproliferative and proapoptotic activities on human ovarian cancer cell lines","volume":"47","author":"Scattolin","year":"2018","journal-title":"Dalton Trans."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.ejmech.2019.06.065","article-title":"Synthesis and in-depth studies on the anticancer activity of novel palladacyclopentadienyl complexes stabilized by N-Heterocyclic carbene ligands","volume":"179","author":"Scattolin","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e4902","DOI":"10.1002\/aoc.4902","article-title":"Palladacyclopentadienyl complexes bearing purine-based N-heterocyclic carbenes: A new class of promising antiproliferative agents against human ovarian cancer","volume":"33","author":"Scattolin","year":"2019","journal-title":"Appl. Organomet. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"11868","DOI":"10.1002\/chem.202002199","article-title":"Palladium(II)-\u03b73 -Allyl Complexes Bearing N-Trifluoromethyl N-Heterocyclic Carbenes: A New Generation of Anticancer Agents that Restrain the Growth of High-Grade Serous Ovarian Cancer Tumoroids","volume":"26","author":"Scattolin","year":"2020","journal-title":"Chemistry"},{"key":"ref_33","first-page":"4057","article-title":"Growth inhibition of HT29 human colon cancer cells by analogues of 1,25-dihydroxyvitamin D3","volume":"54","author":"Shabahang","year":"1994","journal-title":"Cancer Res."},{"key":"ref_34","first-page":"3939","article-title":"Quantification of liver metastases from LS174T human colorectal cancer cells in nude rats by PCR","volume":"19","author":"Stein","year":"1999","journal-title":"Anticancer Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.3748\/wjg.v23.i7.1171","article-title":"Thymoquinone suppresses migration of LoVo human colon cancer cells by reducing prostaglandin E2 induced COX-2 activation","volume":"23","author":"Hsu","year":"2017","journal-title":"World J. Gastroenterol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.3892\/or.2012.2206","article-title":"A new approach to screening cancer stem cells from the U251 human glioblastoma cell line based on cell growth state","volume":"29","author":"Cao","year":"2013","journal-title":"Oncol. Rep."},{"key":"ref_37","first-page":"59","article-title":"Targeting miR-155-5p and miR-221-3p by peptide nucleic acids induces caspase-3 activation and apoptosis in temozolomide-resistant T98G glioblastoma cells","volume":"55","author":"Milani","year":"2019","journal-title":"Int. J. Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"7252013","DOI":"10.1155\/2019\/7252013","article-title":"Role of miR-221\/222 in Tumor Development and the Underlying Mechanism","volume":"2019","author":"Song","year":"2019","journal-title":"J. Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1007\/s13205-020-02326-x","article-title":"MiR-221\/222 promote migration and invasion, and inhibit autophagy and apoptosis by modulating ATG10 in aggressive papillary thyroid carcinoma","volume":"10","author":"Shen","year":"2020","journal-title":"3 Biotech"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"4665","DOI":"10.1002\/jcb.27755","article-title":"MicroRNA-221 regulates osteosarcoma cell proliferation, apoptosis, migration, and invasion by targeting CDKN1B\/p27","volume":"120","author":"Hu","year":"2019","journal-title":"J. Cell. Biochem."},{"key":"ref_41","first-page":"6697","article-title":"miR-221 regulates proliferation and apoptosis of ovarian cancer cells by targeting BMF","volume":"16","author":"Xie","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.3892\/ijo.2017.3898","article-title":"Overexpression of miRNA-221 promotes cell proliferation by targeting the apoptotic protease activating factor-1 and indicates a poor prognosis in ovarian cancer","volume":"50","author":"Li","year":"2017","journal-title":"Int. J. Oncol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"4419","DOI":"10.3892\/ol.2016.5250","article-title":"Downregulation of miR-221\/222 by a microRNA sponge promotes apoptosis in oral squamous cell carcinoma cells through upregulation of PTEN","volume":"12","author":"Zhou","year":"2016","journal-title":"Oncol. Lett."},{"key":"ref_44","first-page":"465","article-title":"Down-regulation of miR-221 inhibits proliferation of pancreatic cancer cells through up-regulation of PTEN, p27(kip1), p57(kip2), and PUMA","volume":"3","author":"Sarkar","year":"2013","journal-title":"Am. J. Cancer Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1186\/1476-4598-9-229","article-title":"MiR-221 and miR-222 target PUMA to induce cell survival in glioblastoma","volume":"9","author":"Zhang","year":"2010","journal-title":"Mol. Cancer"},{"key":"ref_46","first-page":"1621","article-title":"PUMA is a novel target of miR-221\/222 in human epithelial cancers","volume":"37","author":"Zhang","year":"2010","journal-title":"Int. J. Oncol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1053\/j.gastro.2014.06.006","article-title":"A microRNA 221- and 222-mediated feedback loop maintains constitutive activation of NF\u03baB and STAT3 in colorectal cancer cells","volume":"147","author":"Liu","year":"2014","journal-title":"Gastroenterology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"20150354","DOI":"10.1259\/bjr.20150354","article-title":"Glioblastoma multiforme: Emerging treatments and stratification markers beyond new drugs","volume":"88","author":"Seidlitz","year":"2015","journal-title":"Br. J. Radiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e330","DOI":"10.1016\/S1470-2045(17)30345-5","article-title":"European Association for Neuro-Oncology (EANO) guidelines for palliative care in adults with glioblastoma","volume":"18","author":"Pace","year":"2017","journal-title":"Lancet Oncol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/j.biopha.2017.05.125","article-title":"Current status and future therapeutic perspectives of glioblastoma multiforme (GBM) therapy: A review","volume":"92","author":"Anjum","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1158\/0008-5472.CAN-09-1947","article-title":"Drug combination studies and their synergy quantification using the Chou-Talalay method","volume":"70","author":"Chou","year":"2010","journal-title":"Cancer Res."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/15\/5\/1332\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:22:44Z","timestamp":1760124164000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/15\/5\/1332"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,24]]},"references-count":51,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,5]]}},"alternative-id":["pharmaceutics15051332"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics15051332","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,24]]}}}