{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T22:38:06Z","timestamp":1768948686578,"version":"3.49.0"},"reference-count":57,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T00:00:00Z","timestamp":1768780800000},"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 Tecnologia","doi-asserted-by":"publisher","award":["UID\/50006"],"award-info":[{"award-number":["UID\/50006"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Cannabidiol (CBD), the major non-psychotropic cannabinoid derived from Cannabis sativa L., has demonstrated broad anticancer activity across multiple tumor types; however, its effects in renal cell carcinoma (RCC) remain largely undefined. Given the ongoing need for novel therapeutic strategies in RCC, this study provides preliminary mechanistic insights into the cytotoxic, antiproliferative, and redox-modulating properties of CBD in RCC cells and evaluates the influence of serum conditions on its activity. Methods: Human RCC cell lines (Caki-1 and 769-P) and non-tumoral proximal tubular epithelial cells (HK-2) were treated with CBD (1\u2013100 \u00b5M) for up to 48 h under serum-free and serum-supplemented (5%) conditions. Cytotoxic and antiproliferative effects were assessed using the MTT assay, and intracellular reactive oxygen\/nitrogen species (ROS\/RNS) levels were quantified using the H2DCFDA fluorescence assay. Results: CBD significantly decreased RCC cell viability and proliferation in a concentration-dependent manner and induced time-dependent ROS\/RNS accumulation. Comparable sensitivity was observed in non-tumoral HK-2 renal epithelial cells, indicating limited tumor selectivity under the tested in vitro conditions. Notably, these effects were markedly attenuated in the presence of serum, consistent with CBD\u2019s high serum\u2013protein binding and reduced free bioavailability. Conclusions: CBD induces cytotoxic, antiproliferative, and redox-modulating effects in RCC cells in vitro; however, these responses are strongly attenuated by serum, lack tumor selectivity, and require concentrations exceeding clinically achievable plasma levels. Together, these findings delineate major translational limitations for the therapeutic use of CBD in RCC.<\/jats:p>","DOI":"10.3390\/jcm15020792","type":"journal-article","created":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T09:24:34Z","timestamp":1768901074000},"page":"792","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Anticancer Potential of Cannabidiol in Renal Cell Carcinoma: Serum Modulation and Preliminary Mechanistic Insights"],"prefix":"10.3390","volume":"15","author":[{"given":"D\u00e9bora","family":"Sousa","sequence":"first","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o, Inova\u00e7\u00e3o e Desenvolvimento Fernando Pessoa (FP-I3ID), Fernando Pessoa University, Fernando Pessoa Teaching and Culture Foundation, Pra\u00e7a de 9 de Abril 349, 4249-004 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5050-2864","authenticated-orcid":false,"given":"Filipa","family":"Amaro","sequence":"additional","affiliation":[{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy, University of Porto, 4050-313 Porto, Portugal"},{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4073-2121","authenticated-orcid":false,"given":"Ana Margarida","family":"Ara\u00fajo","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio Associado para a Qu\u00edmica Verde\/Rede de Qu\u00edmica e Tecnologia (LAQV\/REQUIMTE), Laboratory of Bromatology and Hydrology, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9884-4751","authenticated-orcid":false,"given":"M\u00e1rcia","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o, Inova\u00e7\u00e3o e Desenvolvimento Fernando Pessoa (FP-I3ID), Fernando Pessoa University, Fernando Pessoa Teaching and Culture Foundation, Pra\u00e7a de 9 de Abril 349, 4249-004 Porto, Portugal"},{"name":"Laborat\u00f3rio Associado para a Qu\u00edmica Verde\/Rede de Qu\u00edmica e Tecnologia (LAQV\/REQUIMTE), Laboratory of Bromatology and Hydrology, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"RISE-Health, Faculty of Health Sciences, Fernando Pessoa University, Fernando Pessoa Teaching and Culture Foundation, Rua Carlos da Maia 296, 4200-150 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1691428","DOI":"10.1155\/2018\/1691428","article-title":"Cannabis sativa L. and Nonpsychoactive Cannabinoids: Their Chemistry and Role against Oxidative Stress, Inflammation, and Cancer","volume":"2018","author":"Pellati","year":"2018","journal-title":"BioMed Res. 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