Utilize este identificador para referenciar este registo: https://hdl.handle.net/1822/73358

TítuloTargeting p53 for melanoma treatment: counteracting tumour proliferation, dissemination and therapeutic resistance
Autor(es)Loureiro, Joana B.
Raimundo, Liliana
Calheiros, Juliana
Carvalho, Carla
Barcherini, Valentina
Lima, Nuno R.
Gomes, Célia
Almeida, Maria Inês
Alves, Marco G.
Costa, José Luís
Santos, Maria M. M.
Saraiva, Lucília
Palavras-chaveMelanoma
Metastasis
Drug resistance
Targeted therapy
p53
Tryptophanol-derived oxazoloisoindolinone
Data1-Abr-2021
EditoraMultidisciplinary Digital Publishing Institute (MDPI)
RevistaCancers
CitaçãoLoureiro, J.B.; Raimundo, L.; Calheiros, J.; Carvalho, C.; Barcherini, V.; Lima, N.R.; Gomes, C.; Almeida, M.I.; Alves, M.G.; Costa, J.L.; Santos, M.M.M.; Saraiva, L. Targeting p53 for Melanoma Treatment: Counteracting Tumour Proliferation, Dissemination and Therapeutic Resistance. Cancers 2021, 13, 1648. https://doi.org/10.3390/cancers13071648
Resumo(s)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–MDM2 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.
TipoArtigo
URIhttps://hdl.handle.net/1822/73358
DOI10.3390/cancers13071648
e-ISSN2072-6694
Versão da editorahttps://www.mdpi.com/2072-6694/13/7/1648
Arbitragem científicayes
AcessoAcesso aberto
Aparece nas coleções:BUM - MDPI

Ficheiros deste registo:
Ficheiro Descrição TamanhoFormato 
cancers-13-01648-v3.pdf48,16 MBAdobe PDFVer/Abrir

Este trabalho está licenciado sob uma Licença Creative Commons Creative Commons

Partilhe no FacebookPartilhe no TwitterPartilhe no DeliciousPartilhe no LinkedInPartilhe no DiggAdicionar ao Google BookmarksPartilhe no MySpacePartilhe no Orkut
Exporte no formato BibTex mendeley Exporte no formato Endnote Adicione ao seu ORCID