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In this work, the effect of chalcones 1\u201318 against the metabolic viability of cervical (HeLa) and prostate (PC-3 and LNCaP) tumor cell lines was tested, to compare the activity against solid and liquid tumor cells. Their effect was also evaluated on the Jurkat cell line. Chalcone 16 showed the highest inhibitory effect on the metabolic viability of the tested tumor cells and was selected for further studies. Recent antitumor therapies include compounds with the ability to influence immune cells on the tumor microenvironment, with immunotherapy being one actual goal in cancer treatment. Therefore, the effect of chalcone 16 on the expression of mTOR, HIF-1\u03b1, IL-1\u03b2, TNF-\u03b1, IL-10, and TGF-\u03b2, after THP-1 macrophage stimulation (none, LPS or IL-4), was evaluated. Chalcone 16 significantly increased the expression of mTORC1, IL-1\u03b2, TNF-\u03b1, and IL-10 of IL-4 stimulated macrophages (that induces an M2 phenotype). HIF-1\u03b1 and TGF-\u03b2 were not significantly affected. Chalcone 16 also decreased nitric oxide production by the RAW 264.7 murine macrophage cell line, this effect probably being due to an inhibition of iNOS expression. These results suggest that chalcone 16 may influence macrophage polarization, inducing the pro-tumoral M2 macrophages (IL-4 stimulated) to adopt a profile closer to the antitumor M1 profile.<\/jats:p>","DOI":"10.3390\/molecules28052159","type":"journal-article","created":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T02:10:46Z","timestamp":1677463846000},"page":"2159","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Antitumor Effect of Chalcone Derivatives against Human Prostate (LNCaP and PC-3), Cervix HPV-Positive (HeLa) and Lymphocyte (Jurkat) Cell Lines and Their Effect on Macrophage Functions"],"prefix":"10.3390","volume":"28","author":[{"given":"Bruno","family":"Horta","sequence":"first","affiliation":[{"name":"Molecular Oncology and Viral Pathology GRP\u2014IC, Portuguese Institute of Oncology of Porto (IPO Porto), Rua Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"ICBAS\u2014School of Medicine and Biomedical Sciences, Port University, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"},{"name":"CBQF\u2014Centre for Biotechnology and Fine Chemistry, Associated Laboratory, Higher School of Biotechnology, Portuguese Catholic University, Rua Diogo Botelho, 1327, 4169-005 Porto, Portugal"}]},{"given":"Joana","family":"Freitas-Silva","sequence":"additional","affiliation":[{"name":"Interdisciplinary Centre of Marine and Environmental Research (CIIMAR), 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 Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"AquaValor\u2014Centro de Valoriza\u00e7\u00e3o e Transfer\u00eancia de Tecnologia da \u00c1gua, Rua J\u00falio Martins, n\u00b01, 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 Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7489-2211","authenticated-orcid":false,"given":"Ana Lu\u00edsa","family":"Teixeira","sequence":"additional","affiliation":[{"name":"Molecular Oncology and Viral Pathology GRP\u2014IC, Portuguese Institute of Oncology of Porto (IPO Porto), Rua Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3010-8373","authenticated-orcid":false,"given":"Rui","family":"Medeiros","sequence":"additional","affiliation":[{"name":"Molecular Oncology and Viral Pathology GRP\u2014IC, Portuguese Institute of Oncology of Porto (IPO Porto), Rua Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"ICBAS\u2014School of Medicine and Biomedical Sciences, Port University, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"},{"name":"FP-I3ID, FP-BHS, Universidade Fernando Pessoa, Pra\u00e7a 9 de Abril, 349, 4249-004 Porto, Portugal"},{"name":"Faculty of Health Sciences, University Fernando Pessoa, Rua Carlos da Maia, 296, 4200-150 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0715-1779","authenticated-orcid":false,"given":"Honorina","family":"Cidade","sequence":"additional","affiliation":[{"name":"Interdisciplinary Centre of Marine and Environmental Research (CIIMAR), 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":"Interdisciplinary Centre of Marine and Environmental Research (CIIMAR), 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 Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"FP-I3ID, FP-BHS, Universidade Fernando Pessoa, Pra\u00e7a 9 de Abril, 349, 4249-004 Porto, Portugal"},{"name":"Faculty of Health Sciences, University Fernando Pessoa, Rua Carlos da Maia, 296, 4200-150 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6174","DOI":"10.1111\/febs.15726","article-title":"Tumor-associated macrophages in immunotherapy","volume":"288","author":"Yan","year":"2021","journal-title":"FEBS J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"188","DOI":"10.3389\/fonc.2020.00188","article-title":"Tumor-Associated Macrophages: Recent Insights and Therapies","volume":"10","author":"Zhou","year":"2020","journal-title":"Front. 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