Tumor growth-arrest effect of tetrahydroquinazoline-derivative human topoisomerase II-alpha inhibitor in HPV-negative head and neck squamous cell carcinoma.

Alternative models Head and neck Tetrahydroquinazoline Topoisomerase

Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
21 Apr 2024
Historique:
received: 08 11 2023
accepted: 12 04 2024
medline: 22 4 2024
pubmed: 22 4 2024
entrez: 21 4 2024
Statut: epublish

Résumé

Oral malignancies continue to have severe morbidity with less than 50% long-term survival despite the advancement in the available therapies. There is a persisting demand for new approaches to establish more efficient strategies for their treatment. In this regard, the human topoisomerase II (topoII) enzyme is a validated chemotherapeutics target, as topoII regulates vital cellular processes such as DNA replication, transcription, recombination, and chromosome segregation in cells. TopoII inhibitors are currently used to treat some neoplasms such as breast and small cells lung carcinomas. Additionally, topoII inhibitors are under investigation for the treatment of other cancer types, including oral cancer. Here, we report the therapeutic effect of a tetrahydroquinazoline derivative (named ARN21934) that preferentially inhibits the alpha isoform of human topoII. The treatment efficacy of ARN21934 has been evaluated in 2D cell cultures, 3D in vitro systems, and in chick chorioallantoic membrane cancer models. Overall, this work paves the way for further preclinical developments of ARN21934 and possibly other topoII alpha inhibitors of this promising chemical class as a new chemotherapeutic approach for the treatment of oral neoplasms.

Identifiants

DOI: 10.1038/s41598-024-59592-5 PMID: 38644364
pubmed: 38644364
doi: 10.1038/s41598-024-59592-5
pii: 10.1038/s41598-024-59592-5
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

9150

Subventions

Organisme : Associazione Italiana per la Ricerca sul Cancro
ID : 29543
Organisme : Associazione Italiana per la Ricerca sul Cancro
ID : 23679
Organisme : Associazione Italiana per la Ricerca sul Cancro
ID : 19852

Informations de copyright

© 2024. The Author(s).

Références

Kim, N. et al. CXCR7 promotes migration and invasion in head and neck squamous cell carcinoma by upregulating TGF-β1/Smad2/3 signaling. Sci. Rep. 9, 1–11 (2019).
Sarogni, P., Mapanao, A. K., Marchetti, S., Kusmic, C. & Voliani, V. A standard protocol for the production and bioevaluation of ethical in vivo models of HPV-Negative head and neck squamous cell carcinoma. ACS Pharmacol. Transl. Sci. 4, 1227–1234 (2021).
pubmed: 34151212 pmcid: 8205242 doi: 10.1021/acsptsci.1c00083
Lango, M. N. Multimodal treatment for head and neck cancer. Surg. Clin. North Am. 89, 43–52 (2009).
pubmed: 19186230 doi: 10.1016/j.suc.2008.09.018
Machiels, J. P. et al. Squamous cell carcinoma of the oral cavity, larynx, oropharynx and hypopharynx: EHNS–ESMO–ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up†. Ann. Oncol. 31, 1462–1475 (2020).
pubmed: 33239190 doi: 10.1016/j.annonc.2020.07.011
Cognetti, D. M., Weber, R. S. & Lai, S. Y. Head and neck Cancer an evolving treatment paradigm. Cancer 113, 1911–1932 (2008).
pubmed: 18798532 doi: 10.1002/cncr.23654
Santi, M., Mapanao, A. K., Biancalana, L., Marchetti, F. & Voliani, V. Ruthenium arene complexes in the treatment of 3D models of head and neck squamous cell carcinomas. Eur. J. Med. Chem. 212, 113143 (2021).
pubmed: 33445155 doi: 10.1016/j.ejmech.2020.113143
Mody, M. D., Rocco, J. W., Yom, S. S., Haddad, R. I. & Saba, N. F. Head and neck cancer. Lancet 398, 2289–2299 (2021).
pubmed: 34562395 doi: 10.1016/S0140-6736(21)01550-6
de Roest, R. H. et al. Disease outcome and associated factors after definitive platinum based chemoradiotherapy for advanced stage HPV-negative head and neck cancer. Radiother. Oncol. 175, 112–121 (2022).
pubmed: 35973619 doi: 10.1016/j.radonc.2022.08.013
Robert, I., Haddad, M. D., Dong, M. & Shin, M. Recent advances in head and neck cancer reconstruction. N. Engl. J. Med. https://doi.org/10.4103/0970-0358.138939 (2008).
doi: 10.4103/0970-0358.138939
Santi, M. et al. Endogenously-Activated ultrasmall-in-nano therapeutics: Assessment on 3D head and neck squamous cell carcinomas. Cancers. 12, 1063 (2020).
pubmed: 32344838 pmcid: 7281743 doi: 10.3390/cancers12051063
Mapanao, A. K., Santi, M. & Voliani, V. Combined chemo-photothermal treatment of three-dimensional head and neck squamous cell carcinomas by gold nano-architectures. J. Colloid Interface Sci. 582, 1003–1011 (2021).
pubmed: 32927167 doi: 10.1016/j.jcis.2020.08.059
Bollimpelli, V. S., Dholaniya, P. S. & Kondapi, A. K. Topoisomerase IIβ and its role in different biological contexts. Arch. Biochem. Biophys. 633, 78–84 (2017).
pubmed: 28669856 doi: 10.1016/j.abb.2017.06.021
Pommier, Y., Nussenzweig, A., Takeda, S. & Austin, C. Human topoisomerases and their roles in genome stability and organization. Nat. Rev. Mol. Cell Biol. 23, 407–427 (2022).
pubmed: 35228717 pmcid: 8883456 doi: 10.1038/s41580-022-00452-3
De Resende, M. F. et al. Prognostication of prostate cancer based on TOP2A protein and gene assessment: TOP2A in prostate cancer. J. Transl. Med. 11, 1–9 (2013).
doi: 10.1186/1479-5876-11-36
Zheng, H. et al. Quantum dot-based immunofluorescent imaging and quantitative detection of TOP2a and prognostic value in triple-negative breast cancer. Int. J. Nanomed. 11, 5519–5529 (2016).
doi: 10.2147/IJN.S111594
Salerno, S. et al. Recent advances in the development of dual topoisomerase I and II inhibitors as anticancer drugs. Curr. Med. Chem. 17, 4270–4290 (2010).
pubmed: 20939813 doi: 10.2174/092986710793361252
Murphy, B. A. et al. Topoisomerase I inhibitors in the treatment of head and neck cancer. Oncology (Williston Park). 15, 47–52 (2001).
pubmed: 11497232
Papanikolaou, V. et al. Topoisomerase IIa protein expression patterns in laryngeal squamous cell carcinoma. Anticancer Res. 40, 807–811 (2020).
pubmed: 32014923 doi: 10.21873/anticanres.14012
Stathopoulos, G. P., Kapranos, N., Manolopoulos, L., Papadimitriou, C. & Adamopoulos, G. Topoisomerase II alpha expression in squamous cell carcinomas of the head and neck. Anticancer Res. 20, 177–82 (2000).
pubmed: 10769652
Ortega, J. A. et al. Novel, potent, and druglike tetrahydroquinazoline inhibitor that is highly selective for human topoisomerase II α over β. J. Med. Chem. 63, 12873–12886 (2020).
pubmed: 33079544 pmcid: 7668297 doi: 10.1021/acs.jmedchem.0c00774
Deweese, J. E. & Osheroff, N. The DNA cleavage reaction of topoisomerase II: Wolf in sheep’s clothing. Nucleic Acids Res. 37, 738–748 (2008).
pubmed: 19042970 pmcid: 2647315 doi: 10.1093/nar/gkn937
Pendleton, M., Lindsey, R. H., Felix, C. A., Grimwade, D. & Osheroff, N. Topoisomerase II and leukemia. Ann. N. Y. Acad. Sci. 1310, 1–13 (2014).
doi: 10.1111/nyas.12358
Sarogni, P. et al. Chorioallantoic membrane tumor models highlight the effects of cisplatin compounds in oral carcinoma treatment. iScience 25, 103980 (2022).
pubmed: 35310338 pmcid: 8924639 doi: 10.1016/j.isci.2022.103980
Mapanao, A. K. et al. Pro-apoptotic and size-reducing effects of protein corona-modulating nano-architectures enclosing platinum prodrug in in vivo oral carcinoma. Biomater. Sci. 10, 6135–6145 (2022).
pubmed: 36069269 doi: 10.1039/D2BM00994C
Santi, M. et al. Hybrid nano-architectures loaded with metal complexes for the co-chemotherapy of head and neck carcinomas. J. Mater. Chem. B 11, 325–334 (2023).
pubmed: 36484416 doi: 10.1039/D2TB01930B
Zamborlin, A. et al. Drug-free hybrid nanoarchitecture modulation of the metastatic behavior of pancreatic ductal adenocarcinoma in alternative in vivo models. ACS Appl. Nano Mater. 6, 22532–22544 (2023).
doi: 10.1021/acsanm.3c05299
Santi, M., Mapanao, A. K., Cappello, V. & Voliani, V. Production of 3D tumor models of head and neck squamous cell carcinomas for nanotheranostics assessment. ACS Biomater. Sci. Eng. 6, 4862–4869 (2020).
pubmed: 33395269 pmcid: 7735655 doi: 10.1021/acsbiomaterials.0c00617
Ribatti, D. The chick embryo chorioallantoic membrane (CAM). A multifaceted experimental model. Mech. Dev. 141, 70–77 (2016).
pubmed: 27178379 doi: 10.1016/j.mod.2016.05.003
Livak, K. J. & Schmittgen, T. D. Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT method. Methods 25, 402–408 (2001).
pubmed: 11846609 doi: 10.1006/meth.2001.1262
Pflüger, K. H. et al. Pharmacokinetics of etoposide: Correlation of pharmacokinetic parameters with clinical conditions. Cancer Chemother. Pharmacol. 31, 350–356 (1993).
pubmed: 8431968 doi: 10.1007/BF00686147
Eastman, A. Improving anticancer drug development begins with cell culture: Misinformation perpetrated by the misuse of cytotoxicity assays. Oncotarget 8, 8854–8866 (2017).
pubmed: 27750219 doi: 10.18632/oncotarget.12673
Gomes, R. N., Manuel, F. & Nascimento, D. S. The bright side of fibroblasts: Molecular signature and regenerative cues in major organs. npj Regen. Med. 8, 42 (2023).
pubmed: 37550291 pmcid: 10406803 doi: 10.1038/s41536-023-00319-x
Mapanao, A. K. A. K. & Voliani, V. Three-dimensional tumor models: Promoting breakthroughs in nanotheranostics translational research. Appl. Mater. Today 19, 100552 (2020).
doi: 10.1016/j.apmt.2019.100552
Białkowska, K., Komorowski, P., Bryszewska, M. & Miłowska, K. Spheroids as a type of three-dimensional cell cultures—examples of methods of preparation and the most important application. Int. J. Mol. Sci. 21, 1–17 (2020).
doi: 10.3390/ijms21176225
Nair, A. & Jacob, S. A simple practice guide for dose conversion between animals and human. J. Basic Clin. Pharm. 7, 27 (2016).
pubmed: 27057123 pmcid: 4804402 doi: 10.4103/0976-0105.177703
Hickman, J. A. Apoptosis induced by anticancer drugs. Cancer Metastasis Rev. 11, 121–139 (1992).
pubmed: 1327566 doi: 10.1007/BF00048059
Chang, B. D. et al. Molecular determinants of terminal growth arrest induced in tumor cells by a chemotherapeutic agent. PNAS 99, 389–394 (2002).
pubmed: 11752408 doi: 10.1073/pnas.012602599
Strzalka, W. & Ziemienowicz, A. Proliferating cell nuclear antigen (PCNA): A key factor in DNA replication and cell cycle regulation. Ann. Bot. 107, 1127–1140 (2011).
pubmed: 21169293 doi: 10.1093/aob/mcq243
Liu, J., Qu, L., Meng, L. & Shou, C. Topoisomerase inhibitors promote cancer cell motility via ROS-mediated activation of JAK2-STAT1-CXCL1 pathway. J. Exp. Clin. Cancer Res. https://doi.org/10.1186/s13046-019-1353-2 (2019).
doi: 10.1186/s13046-019-1353-2 pubmed: 31888685 pmcid: 6936093
Benazzi, C. et al. Angiogenesis in spontaneous tumors and implications for comparative tumor biology. Sci. World J. 2014, 1–16 (2014).
doi: 10.1155/2014/919570
Patel, K. R. et al. VEGFA isoforms play a vital role in oral cancer progression. Tumor Biol. 36, 6321–6332 (2015).
doi: 10.1007/s13277-015-3318-1
Xu, X. et al. Indenoisoquinoline derivatives as topoisomerase I inhibitors that suppress angiogenesis by affecting the HIF signaling pathway. Biomed. Pharmacother. 67, 715–722 (2013).
pubmed: 23932721 doi: 10.1016/j.biopha.2013.06.004
Clere, N., Faure, S., Helesbeux, J. J., Duval, O. & Andriantsitohaina, R. Paradoxical effects of ethoxidine, a topoisomerase I inhibitor, in the cellular processes leading to angiogenesis on endothelial cells. Carcinogenesis 32, 286–295 (2011).
pubmed: 21135154 doi: 10.1093/carcin/bgq260
Bologna-Molina, R., Mosqueda-Taylor, A., Molina-Frechero, N., Mori-Estevez, A. D. & Sánchez-Acuña, G. Comparison of the value of PCNA and Ki-67 as markers of cell proliferation in ameloblastic tumors. Med. Oral Patol. Oral Cir. Bucal 18, e174–e179 (2013).
pubmed: 23229269 doi: 10.4317/medoral.18573
Slade, D. Maneuvers on PCNA rings during DNA replication and repair. Genes. 9, 416 (2018).
pubmed: 30126151 pmcid: 6116012 doi: 10.3390/genes9080416
Server, E. A. et al. Predictive role of ki-67 and proliferative-cell nuclear antigen (Pcna) in recurrent cholesteatoma. J. Int. Adv. Otol. 15, 38–42 (2019).
doi: 10.5152/iao.2018.4976
Skok, Ž, Zidar, N., Kikelj, D. & Ilaš, J. Dual inhibitors of human DNA topoisomerase II and other cancer-related targets. J. Med. Chem. 63, 884–904 (2020).
pubmed: 31592646 doi: 10.1021/acs.jmedchem.9b00726
Gonnelli, A. et al. A bioconvergence study on platinum-free concurrent chemoradiotherapy for the treatment of HPV-negative head and neck carcinoma. Artif. Cells Nanomedicine, Biotechnol. 52, 122–129 (2024).
doi: 10.1080/21691401.2024.2309233

Auteurs

Patrizia Sarogni (P)

Center for Nanotechnology Innovation@ NEST, Istituto Italiano di Tecnologia, Piazza San Silvestro, 12, 56126, Pisa, Italy.
Molecular Modeling and Drug Discovery Lab, Istituto Italiano di Tecnologia, via Morego, 30, 16163, Genoa, Italy.

Nicoletta Brindani (N)

Molecular Modeling and Drug Discovery Lab, Istituto Italiano di Tecnologia, via Morego, 30, 16163, Genoa, Italy.

Agata Zamborlin (A)

Center for Nanotechnology Innovation@ NEST, Istituto Italiano di Tecnologia, Piazza San Silvestro, 12, 56126, Pisa, Italy.
NEST - Scuola Normale Superiore, Piazza San Silvestro, 12, 56126, Pisa, Italy.
Ghent Research Group on Nanomedicines, Department of Pharmaceutics, Ghent University, Ottergemsesteenweg 460, B-9000, Ghent, Belgium.

Alessandra Gonnelli (A)

Center for Nanotechnology Innovation@ NEST, Istituto Italiano di Tecnologia, Piazza San Silvestro, 12, 56126, Pisa, Italy.
Department of Translational Medicine, University of Pisa, 56126, Pisa, Italy.

Michele Menicagli (M)

Fondazione Pisana per la Scienza ONLUS, via Ferruccio Giovannini, 13, 56017, S. Giuliano Terme, Italy.

Ana Katrina Mapanao (AK)

Center for Radiopharmaceutical Sciences, Paul Scherrer Institute (PSI), 5232, Villigen, Switzerland.

Federico Munafò (F)

Molecular Modeling and Drug Discovery Lab, Istituto Italiano di Tecnologia, via Morego, 30, 16163, Genoa, Italy.

Marco De Vivo (M)

Molecular Modeling and Drug Discovery Lab, Istituto Italiano di Tecnologia, via Morego, 30, 16163, Genoa, Italy. marco.devivo@iit.it.

Valerio Voliani (V)

Center for Nanotechnology Innovation@ NEST, Istituto Italiano di Tecnologia, Piazza San Silvestro, 12, 56126, Pisa, Italy. valerio.voliani@unige.it.
Department of Pharmacy, School of Medical and Pharmaceutical Sciences, University of Genoa, Viale Cembrano 4, 16148, Genoa, Italy. valerio.voliani@unige.it.

Classifications MeSH