{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T05:03:28Z","timestamp":1764047008934,"version":"build-2065373602"},"reference-count":32,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,6,18]],"date-time":"2021-06-18T00:00:00Z","timestamp":1623974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UID\/Multi\/04546\/2019","UIDP\/04423\/2020","POCI-01-0145-FEDER-016790; Project 3599"],"award-info":[{"award-number":["UID\/Multi\/04546\/2019","UIDP\/04423\/2020","POCI-01-0145-FEDER-016790; Project 3599"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Xanthone derivatives have shown promising antitumor properties, and 1-carbaldehyde-3,4-dimethoxyxanthone (1) has recently emerged as a potent tumor cell growth inhibitor. In this study, its effect was evaluated (MTT viability assay) against a new panel of cancer cells, namely cervical cancer (HeLa), androgen-sensitive (LNCaP) and androgen-independent (PC-3) prostate cancer, and nonsolid tumor derived cancer (Jurkat) cell lines. The effect of xanthone 1 on macrophage functions was also evaluated. The effect of xanthone 1-conditioned THP-1 human macrophage supernatants on the metabolic viability of cervical and prostate cancer cell lines was determined along with its interference with cytokine expression characteristic of M1 profile (IL-1 \u2264 \u03b2; TNF-\u03b1) or M2 profile (IL-10; TGF-\u03b2) (PCR and ELISA). Nitric oxide (NO) production by murine RAW264.7 macrophages was quantified by Griess reaction. Xanthone 1 (20 \u03bcM) strongly inhibited the metabolic activity of the cell lines and was significantly more active against prostate cell lines compared to HeLa (p &lt; 0.05). Jurkat was the cell most sensitive to the effect of xanthone 1. Compound 1-conditioned IL-4-stimulated THP-1 macrophage supernatants significantly (p &lt; 0.05) inhibited the metabolic activity of HeLa, LNCaP, and PC-3. Xanthone 1 did not significantly affect the expression of cytokines by THP-1 macrophages. The inhibiting effect of compound 1 observed on the production of NO by RAW 264.7 macrophages was moderate. In conclusion, 1-carbaldehyde-3,4-dimethoxyxanthone (1) decreases the metabolic activity of cancer cells and seems to be able to modulate macrophage functions.<\/jats:p>","DOI":"10.3390\/molecules26123721","type":"journal-article","created":{"date-parts":[[2021,6,18]],"date-time":"2021-06-18T11:19:20Z","timestamp":1624015160000},"page":"3721","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Effect of 1-Carbaldehyde-3,4-dimethoxyxanthone on Prostate and HPV-18 Positive Cervical Cancer Cell Lines and on Human THP-1 Macrophages"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3010-8373","authenticated-orcid":false,"given":"Rui","family":"Medeiros","sequence":"first","affiliation":[{"name":"Molecular Oncology and Viral Pathology GRP\u2014IC, Portuguese Institute of Oncology of Porto (IPO Porto), Rua Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"FP-ENAS Research Unit, UFP Energy, Environment and Health Research Unit, CEBIMED, Biomedical Research Centre, Fernando Pessoa University, Pra\u00e7a 9 de Abril, 349, 4249-004 Porto, Portugal"},{"name":"Faculty of Health Sciences, Fernando Pessoa University, Rua Carlos da Maia, 296, 4200-150 Porto, Portugal"},{"name":"ICBAS\u2014Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2769-8958","authenticated-orcid":false,"given":"Bruno","family":"Horta","sequence":"additional","affiliation":[{"name":"Molecular Oncology and Viral Pathology GRP\u2014IC, Portuguese Institute of Oncology of Porto (IPO Porto), Rua Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"ICBAS\u2014Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"},{"name":"Associated Laboratory, CBQF\u2014Centre for Biotechnology and Fine Chemistry, Higher School of Biotechnology, Portuguese Catholic University, Rua Diogo Botelho, 1327, 4169-005 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0235-4991","authenticated-orcid":false,"given":"Joana","family":"Freitas-Silva","sequence":"additional","affiliation":[{"name":"CIIMAR\/CIMAR, Interdisciplinary Centre of Marine and Environmental Research, Terminal de Cruzeiros do Porto de Leix\u00f5es, Av. General Norton de Matos s\/n, 4450-208 Matosinhos, Portugal"}]},{"given":"Jani","family":"Silva","sequence":"additional","affiliation":[{"name":"Molecular Oncology and Viral Pathology GRP\u2014IC, Portuguese Institute of Oncology of Porto (IPO Porto), Rua Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"AquaValor\u2014Centro de Valoriza\u00e7\u00e3o e Transfer\u00eancia de Tecnologia da \u00c1gua, Rua Dr. J\u00falio Martins, n\u00ba1, 5400-342 Chaves, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4993-4467","authenticated-orcid":false,"given":"Francisca","family":"Dias","sequence":"additional","affiliation":[{"name":"Molecular Oncology and Viral Pathology GRP\u2014IC, Portuguese Institute of Oncology of Porto (IPO Porto), Rua Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5397-4672","authenticated-orcid":false,"given":"Em\u00edlia","family":"Sousa","sequence":"additional","affiliation":[{"name":"CIIMAR\/CIMAR, Interdisciplinary Centre of Marine and Environmental Research, Terminal de Cruzeiros do Porto de Leix\u00f5es, Av. General Norton de Matos s\/n, 4450-208 Matosinhos, Portugal"},{"name":"Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4676-1409","authenticated-orcid":false,"given":"Madalena","family":"Pinto","sequence":"additional","affiliation":[{"name":"CIIMAR\/CIMAR, Interdisciplinary Centre of Marine and Environmental Research, Terminal de Cruzeiros do Porto de Leix\u00f5es, Av. General Norton de Matos s\/n, 4450-208 Matosinhos, Portugal"},{"name":"Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"}]},{"given":"F\u00e1tima","family":"Cerqueira","sequence":"additional","affiliation":[{"name":"Molecular Oncology and Viral Pathology GRP\u2014IC, Portuguese Institute of Oncology of Porto (IPO Porto), Rua Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"FP-ENAS Research Unit, UFP Energy, Environment and Health Research Unit, CEBIMED, Biomedical Research Centre, Fernando Pessoa University, Pra\u00e7a 9 de Abril, 349, 4249-004 Porto, Portugal"},{"name":"Faculty of Health Sciences, Fernando Pessoa University, Rua Carlos da Maia, 296, 4200-150 Porto, Portugal"},{"name":"CIIMAR\/CIMAR, Interdisciplinary Centre of Marine and Environmental Research, Terminal de Cruzeiros do Porto de Leix\u00f5es, Av. General Norton de Matos s\/n, 4450-208 Matosinhos, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1080\/10611860400027717","article-title":"Improvement of the inhibitory effect of xanthones on NO production by encapsulation in PLGA nanocapsules","volume":"13","author":"Teixeira","year":"2005","journal-title":"J. Drug Target."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3725","DOI":"10.1016\/S0968-0896(02)00379-6","article-title":"Xanthones as inhibitors of growth of human cancer cell lines and Their effects on the proliferation of human lymphocytes in vitro","volume":"10","author":"Pedro","year":"2002","journal-title":"Bioorg. Med. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Silva, V., Cerqueira, F., Nazareth, N., Medeiros, R., Sarmento, A., Sousa, E., and Pinto, M. (2019). 1,2-Dihydroxyxanthone: Effect on A375-C5 Melanoma Cell Growth Associated with Interference with THP-1 Human Macrophage Activity. Pharmaceuticals, 12.","DOI":"10.3390\/ph12020085"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Pinto, M.M.M., Palmeira, A., Fernandes, C., Resende, D.I.S.P., Sousa, E., Cidade, H., Tiritan, M.E., Correia-da-Silva, M., and Cravo, S. (2021). From Natural Products to New Synthetic Small Molecules: A Journey through the World of Xanthones. Molecules, 26.","DOI":"10.3390\/molecules26020431"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"102226","DOI":"10.1016\/j.jddst.2020.102226","article-title":"Development of lipid nanoparticles containing the xanthone LEM2 for topical treatment of melanoma","volume":"61","author":"Malta","year":"2021","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.canlet.2019.01.014","article-title":"New inhibitor of the TAp73 interaction with MDM2 and mutant p53 with promising antitumor activity against neuroblastoma","volume":"446","author":"Gomes","year":"2019","journal-title":"Cancer Lett."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3241","DOI":"10.1158\/1078-0432.CCR-16-3122","article-title":"The Promise of Targeting Macrophages in Cancer Therapy","volume":"23","author":"Brown","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"761","DOI":"10.7150\/jca.17648","article-title":"Role of tumor microenvironment in tumorigenesis","volume":"8","author":"Wang","year":"2017","journal-title":"J. Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"49","DOI":"10.3389\/fonc.2018.00049","article-title":"Targeting Macrophages in Cancer: From Bench to Bedside","volume":"8","author":"Poh","year":"2018","journal-title":"Front. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1038\/bjc.2017.356","article-title":"TAMeless traitors: Macrophages in cancer progression and metastasis","volume":"117","author":"Aras","year":"2017","journal-title":"Br. J. Cancer"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1002\/ijgo.12320","article-title":"Associations between intratumoral and peritumoral M2 macrophage counts and cervical squamous cell carcinoma invasion patterns","volume":"139","author":"Li","year":"2017","journal-title":"Int. J. Gynaecol. Obstet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2625","DOI":"10.3892\/ol.2016.5014","article-title":"Co-evolution of tumor-associated macrophages and tumor neo-vessels during cervical cancer invasion","volume":"12","author":"Jiang","year":"2016","journal-title":"Oncol. Lett."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e2636","DOI":"10.1097\/MD.0000000000002636","article-title":"High Infiltration of Tumor-Associated Macrophages Influences Poor Prognosis in Human Gastric Cancer Patients, Associates with the Phenomenon of EMT","volume":"95","author":"Zhang","year":"2016","journal-title":"Medicine"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"486798","DOI":"10.1155\/2014\/486798","article-title":"The Role of M1 and M2 Macrophages in Prostate Cancer in relation to Extracapsular Tumor Extension and Biochemical Recurrence after Radical Prostatectomy","volume":"2014","author":"Lanciotti","year":"2014","journal-title":"Biomed. Res. Int."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"48436","DOI":"10.18632\/oncotarget.17061","article-title":"Redirecting tumor-associated macrophages to become tumoricidal effectors as a novel strategy for cancer therapy","volume":"8","author":"Zheng","year":"2017","journal-title":"Oncotarget"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"9720912","DOI":"10.1155\/2016\/9720912","article-title":"New Mechanisms of Tumor-Associated Macrophages on Promoting Tumor Progression: Recent Research Advances and Potential Targets for Tumor Immunotherapy","volume":"2016","author":"Guo","year":"2016","journal-title":"J. Immunol. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/cdd.2012.123","article-title":"TAp73 is required for macrophage-mediated innate immunity and the resolution of inflammatory responses","volume":"20","author":"Tomasini","year":"2013","journal-title":"Cell Death Differ."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1159\/000474185","article-title":"Epidemiology of Prostate Cancer","volume":"30","author":"Dijkman","year":"1996","journal-title":"Eur. Urol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1038\/bjc.2011.301","article-title":"Trends in breast, ovarian and cervical cancer incidence in Mumbai, India over a 30-year period, 1976\u20132005: An age\u2013period\u2013cohort analysis","volume":"105","author":"Dhillon","year":"2011","journal-title":"Br. J. Cancer"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1158\/1541-7786.MCR-07-0297","article-title":"Role of activating transcription factor 3 on TAp73 stability and apoptosis in paclitaxel-treated cervical cancer cells","volume":"6","author":"Oh","year":"2008","journal-title":"MCR"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.coph.2009.04.008","article-title":"Anti-inflammatory and pro-inflammatory roles of TGF-beta, IL-10, and IL-22 in immunity and autoimmunity","volume":"9","author":"Sanjabi","year":"2009","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2418","DOI":"10.1128\/IAI.68.5.2418-2423.2000","article-title":"Transforming growth factor-beta inhibits lipopolysaccharide-stimulated expression of inflammatory cytokines in mouse macrophages through downregulation of activation protein 1 and CD14 receptor expression","volume":"68","author":"Imai","year":"2000","journal-title":"Infect. Immun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1038\/sj.cr.7290133","article-title":"The role of nitric oxide in cancer","volume":"12","author":"Xu","year":"2002","journal-title":"Cell Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/S0304-3835(02)00118-0","article-title":"Endothelial nitric oxide synthase gene polymorphisms and the shedding of circulating tumour cells in the blood of prostate cancer patients","volume":"10","author":"Medeiros","year":"2003","journal-title":"Cancer Lett."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e2017089118","DOI":"10.1073\/pnas.2017089118","article-title":"TAp73 represses NF-\u03baB-mediated recruitment of tumor-associated macrophages in breast cancer","volume":"9","author":"Wolfsberger","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Lemos, A., Gomes, A.S., Loureiro, J.B., Brand\u00e3o, P., Palmeira, A., Pinto, M.M.M., Saraiva, L., and Sousa, M.E. (2019). Synthesis, Biological Evaluation, and In Silico Studies of Novel Aminated Xanthones as Potential p53-Activating Agents. Molecules, 24.","DOI":"10.3390\/molecules24101975"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0022-1759(83)90303-4","article-title":"Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays","volume":"65","author":"Mosmann","year":"1983","journal-title":"J. Immunol. Methods"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"451","DOI":"10.4103\/0250-474X.108421","article-title":"Antiproliferative Effect of Solanum nigrum on Human Leukemic Cell Lines","volume":"74","author":"Gabrani","year":"2012","journal-title":"Indian J. Pharm. Sci."},{"key":"ref_29","first-page":"2143","article-title":"Synergy of BID with doxorubicin in the killing of cancer cells","volume":"33","author":"Orzechowska","year":"2015","journal-title":"Oncol. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.intimp.2014.08.002","article-title":"THP-1 cell line: An in vitro cell model for immune modulation approach","volume":"23","author":"Chanput","year":"2014","journal-title":"Int. Immunopharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1002\/mnfr.201100715","article-title":"\u03b2-Glucans are involved in immune-modulation of THP-1 macrophages","volume":"56","author":"Chanput","year":"2012","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3155","DOI":"10.3390\/molecules17033155","article-title":"Inhibitory Effect of Astragalus Polysaccharides on Lipopolysaccharide-Induced TNF-\u03b1 and IL-1\u03b2 Production in THP-1 Cells","volume":"17","author":"He","year":"2012","journal-title":"Molecules"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/12\/3721\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:18:16Z","timestamp":1760163496000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/12\/3721"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,18]]},"references-count":32,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["molecules26123721"],"URL":"https:\/\/doi.org\/10.3390\/molecules26123721","relation":{},"ISSN":["1420-3049"],"issn-type":[{"type":"electronic","value":"1420-3049"}],"subject":[],"published":{"date-parts":[[2021,6,18]]}}}