{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T21:28:41Z","timestamp":1775597321575,"version":"3.50.1"},"reference-count":61,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T00:00:00Z","timestamp":1617235200000},"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\/QUI\/50006\/2020"],"award-info":[{"award-number":["UID\/QUI\/50006\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Melanoma is the deadliest form of skin cancer, primarily due to its high metastatic propensity and therapeutic resistance in advanced stages. The frequent inactivation of the p53 tumour suppressor protein in melanomagenesis may predict promising outcomes for p53 activators in melanoma therapy. Herein, we aimed to investigate the antitumor potential of the p53-activating agent SLMP53-2 against melanoma. Two- and three-dimensional cell cultures and xenograft mouse models were used to unveil the antitumor activity and the underlying molecular mechanism of SLMP53-2 in melanoma. SLMP53-2 inhibited the growth of human melanoma cells in a p53-dependent manner through induction of cell cycle arrest and apoptosis. Notably, SLMP53-2 induced p53 stabilization by disrupting the p53\u2013MDM2 interaction, enhancing p53 transcriptional activity. It also promoted the expression of p53-regulated microRNAs (miRNAs), including miR-145 and miR-23a. Moreover, it displayed anti-invasive and antimigratory properties in melanoma cells by inhibiting the epithelial-to-mesenchymal transition (EMT), angiogenesis and extracellular lactate production. Importantly, SLMP53-2 did not induce resistance in melanoma cells. Additionally, it synergized with vemurafenib, dacarbazine and cisplatin, and resensitized vemurafenib-resistant cells. SLMP53-2 also exhibited antitumor activity in human melanoma xenograft mouse models by repressing cell proliferation and EMT while stimulating apoptosis. This work discloses the p53-activating agent SLMP53-2 which has promising therapeutic potential in advanced melanoma, either as a single agent or in combination therapy. By targeting p53, SLMP53-2 may counteract major features of melanoma aggressiveness.<\/jats:p>","DOI":"10.3390\/cancers13071648","type":"journal-article","created":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T07:23:17Z","timestamp":1617261797000},"page":"1648","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Targeting p53 for Melanoma Treatment: Counteracting Tumour Proliferation, Dissemination and Therapeutic Resistance"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1975-1125","authenticated-orcid":false,"given":"Joana B.","family":"Loureiro","sequence":"first","affiliation":[{"name":"LAQV\/REQUIMTE, Laborat\u1f79rio de Microbiologia, Departamento de Ci\u00eancias Biol\u1f79gicas, Faculdade de Farm\u00e1cia, Universidade do Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9003-2601","authenticated-orcid":false,"given":"Liliana","family":"Raimundo","sequence":"additional","affiliation":[{"name":"LAQV\/REQUIMTE, Laborat\u1f79rio de Microbiologia, Departamento de Ci\u00eancias Biol\u1f79gicas, Faculdade de Farm\u00e1cia, Universidade do Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5895-6951","authenticated-orcid":false,"given":"Juliana","family":"Calheiros","sequence":"additional","affiliation":[{"name":"LAQV\/REQUIMTE, Laborat\u1f79rio de Microbiologia, Departamento de Ci\u00eancias Biol\u1f79gicas, Faculdade de Farm\u00e1cia, Universidade do Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1844-071X","authenticated-orcid":false,"given":"Carla","family":"Carvalho","sequence":"additional","affiliation":[{"name":"LAQV\/REQUIMTE, Laborat\u1f79rio de Microbiologia, Departamento de Ci\u00eancias Biol\u1f79gicas, Faculdade de Farm\u00e1cia, Universidade do Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4597-7419","authenticated-orcid":false,"given":"Valentina","family":"Barcherini","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8614-9732","authenticated-orcid":false,"given":"Nuno R.","family":"Lima","sequence":"additional","affiliation":[{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR), Institute of Pharmacology and Experimental Therapeutics, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), 3000-548 Coimbra, Portugal"}]},{"given":"C\u00e9lia","family":"Gomes","sequence":"additional","affiliation":[{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR), Institute of Pharmacology and Experimental Therapeutics, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), 3000-548 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2072-8587","authenticated-orcid":false,"given":"Maria In\u00eas","family":"Almeida","sequence":"additional","affiliation":[{"name":"ICBAS\u2014Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"},{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, Rua Alfredo Allen, 4200-135 Porto, Portugal"},{"name":"INEB\u2014Instituto de Engenharia Biom\u00e9dica, Universidade do Porto, Rua Alfredo Allen, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7635-783X","authenticated-orcid":false,"given":"Marco G.","family":"Alves","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Unit for Multidisciplinary Research in Biomedicine (UMIB), Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7132-4094","authenticated-orcid":false,"given":"Jos\u00e9 Lu\u00eds","family":"Costa","sequence":"additional","affiliation":[{"name":"ICBAS\u2014Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135 Porto, Portugal"},{"name":"Faculty of Medicine, University of Porto, Pra\u00e7a de Gomes Teixeira, 4099-002 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2239-9353","authenticated-orcid":false,"given":"Maria M. M.","family":"Santos","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9531-4939","authenticated-orcid":false,"given":"Luc\u00edlia","family":"Saraiva","sequence":"additional","affiliation":[{"name":"LAQV\/REQUIMTE, Laborat\u1f79rio de Microbiologia, Departamento de Ci\u00eancias Biol\u1f79gicas, Faculdade de Farm\u00e1cia, Universidade do Porto, 4050-313 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"35","DOI":"10.2147\/ITT.S134842","article-title":"Melanoma treatment in review","volume":"7","author":"Domingues","year":"2018","journal-title":"Immunotargets"},{"key":"ref_2","unstructured":"Ferlay, J., Ervik, M., Lam, F., Colombet, M., Mery, L., Pi\u00f1eros, M., Znaor, A., Soerjomataram, I., and Bray, F. 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