{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T10:51:10Z","timestamp":1770893470886,"version":"3.50.1"},"reference-count":73,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T00:00:00Z","timestamp":1715731200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia (FCT) to i3S. F.C. thanks Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia and Minist\u00e9rio da Ci\u00eancia, Tecnologia e Ensino Superior (FCT) for her PhD fellowship","award":["2021.09409.BD"],"award-info":[{"award-number":["2021.09409.BD"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia (FCT) to i3S. F.C. thanks Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia and Minist\u00e9rio da Ci\u00eancia, Tecnologia e Ensino Superior (FCT) for her PhD fellowship","award":["CEECIND\/08492\/2022"],"award-info":[{"award-number":["CEECIND\/08492\/2022"]}]},{"name":"Scientific Employment Stimulus\u2014Individual Call","award":["2021.09409.BD"],"award-info":[{"award-number":["2021.09409.BD"]}]},{"name":"Scientific Employment Stimulus\u2014Individual Call","award":["CEECIND\/08492\/2022"],"award-info":[{"award-number":["CEECIND\/08492\/2022"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Human malignancies are one of the major health-related issues throughout the world and are anticipated to rise in the future. Despite huge investments made in anticancer drug development, limited success has been obtained and the average number of FDA approvals per year is declining. So, an increasing interest in drug repurposing exists. Metformin (MET) and aspirin (ASP) possess anticancer properties. This work aims to test the effect of these two drugs in combination on colorectal cancer (CRC) cells in vitro. The effects of MET and\/or ASP on cell proliferation, viability, migratory ability, anchorage-independent growth ability (colony formation), and nutrient uptake were determined in two (HT-29 and Caco-2) human CRC cell lines. Individually, MET and ASP possessed antiproliferative, cytotoxic, and antimigratory effects and reduced colony formation in HT-29 cells (BRAF- and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit \u03b1 (PI3KCA)-mutant), although MET did not affect either 3H-deoxy-D-glucose or 14C-butyrate uptake and lactate production, and ASP caused only a small decrease in 14C-butyrate uptake. Moreover, in these cells, the combination of MET and ASP resulted in a tendency to an increase in the cytotoxic effect and in a potentiation of the inhibitory effect on colony formation, although no additive antiproliferative and antimigratory effects, and no effect on nutrient uptake and lactate production were observed. In contrast, MET and ASP, both individually and in combination, were almost devoid of effects on Caco-2 cells (BRAF- and PI3KCA-wild type). We suggest that inhibition of PI3K is the common mechanism involved in the anti-CRC effect of both MET, ASP and their combination and, therefore, that the combination of MET + ASP may especially benefit PI3KCA-mutant CRC cases, which currently have a poor prognostic.<\/jats:p>","DOI":"10.3390\/ijms25105381","type":"journal-article","created":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T03:35:55Z","timestamp":1715744155000},"page":"5381","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Additive Cytotoxic and Colony-Formation Inhibitory Effects of Aspirin and Metformin on PI3KCA-Mutant Colorectal Cancer Cells"],"prefix":"10.3390","volume":"25","author":[{"given":"Joana","family":"Gon\u00e7alves","sequence":"first","affiliation":[{"name":"Unit of Biochemistry, Department of Biomedicine, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"}]},{"given":"Sara","family":"Pinto","sequence":"additional","affiliation":[{"name":"Unit of Biochemistry, Department of Biomedicine, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"}]},{"given":"Francisca","family":"Carmo","sequence":"additional","affiliation":[{"name":"Unit of Biochemistry, Department of Biomedicine, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"}]},{"given":"Cl\u00e1udia","family":"Silva","sequence":"additional","affiliation":[{"name":"LAQV\/REQUIMTE, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, 4050-453 Porto, Portugal"}]},{"given":"Nelson","family":"Andrade","sequence":"additional","affiliation":[{"name":"Unit of Biochemistry, Department of Biomedicine, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"},{"name":"LAQV\/REQUIMTE, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, 4050-453 Porto, Portugal"},{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), University of Porto, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0525-3416","authenticated-orcid":false,"given":"F\u00e1tima","family":"Martel","sequence":"additional","affiliation":[{"name":"Unit of Biochemistry, Department of Biomedicine, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"},{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), University of Porto, 4200-135 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21654","article-title":"Cancer Statistics","volume":"71","author":"Siegel","year":"2021","journal-title":"CA Cancer J. 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