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SIRT6 pharmacological inhibition delays skin cancer progression in the squamous cell carcinoma.
Abbotto, Elena; Miro, Caterina; Piacente, Francesco; Salis, Annalisa; Murolo, Melania; Nappi, Annarita; Millo, Enrico; Russo, Eleonora; Cichero, Elena; Sturla, Laura; Del Rio, Alberto; De Flora, Antonio; Nencioni, Alessio; Dentice, Monica; Bruzzone, Santina.
Afiliação
  • Abbotto E; DIMES, Section of Biochemistry, University of Genova, Viale Benedetto XV, 1, 16132 Genova, Italy.
  • Miro C; Department of Clinical Medicine and Surgery, University of Napoli Federico II, Via Pansini, 5, 80131 Napoli, Italy.
  • Piacente F; DIMES, Section of Biochemistry, University of Genova, Viale Benedetto XV, 1, 16132 Genova, Italy.
  • Salis A; DIMES, Section of Biochemistry, University of Genova, Viale Benedetto XV, 1, 16132 Genova, Italy.
  • Murolo M; Department of Clinical Medicine and Surgery, University of Napoli Federico II, Via Pansini, 5, 80131 Napoli, Italy.
  • Nappi A; Department of Clinical Medicine and Surgery, University of Napoli Federico II, Via Pansini, 5, 80131 Napoli, Italy.
  • Millo E; DIMES, Section of Biochemistry, University of Genova, Viale Benedetto XV, 1, 16132 Genova, Italy.
  • Russo E; Department of Pharmacy, University of Genova, Viale Benedetto XV, 3, 16132 Genova, Italy.
  • Cichero E; Department of Pharmacy, University of Genova, Viale Benedetto XV, 3, 16132 Genova, Italy.
  • Sturla L; DIMES, Section of Biochemistry, University of Genova, Viale Benedetto XV, 1, 16132 Genova, Italy.
  • Del Rio A; Innovamol Consulting Srl, Strada San Faustino 167, 41126 Modena, Italy; Institute of Organic Synthesis and Photoreactivity (ISOF), National Research Council of Italy (CNR), Via P. Gobetti 101, I-40129 Bologna, Italy.
  • De Flora A; DIMES, Section of Biochemistry, University of Genova, Viale Benedetto XV, 1, 16132 Genova, Italy.
  • Nencioni A; Department of Internal Medicine, University of Genova, Viale Benedetto XV, 6, 16132 Genova, Italy; IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, 16132 Genova, Italy. Electronic address: alessio.nencioni@unige.it.
  • Dentice M; Department of Clinical Medicine and Surgery, University of Napoli Federico II, Via Pansini, 5, 80131 Napoli, Italy.
  • Bruzzone S; DIMES, Section of Biochemistry, University of Genova, Viale Benedetto XV, 1, 16132 Genova, Italy; IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, 16132 Genova, Italy. Electronic address: santina.bruzzone@unige.it.
Biomed Pharmacother ; 166: 115326, 2023 10.
Article em En | MEDLINE | ID: mdl-37611438
ABSTRACT
Sirtuin 6 (SIRT6) has a critical role in cutaneous Squamous Cell Carcinoma (cSCC) SIRT6 silencing in skin SCC cells has pro-differentiating effects and SIRT6 deletion abrogated DMBA-TPA-induced skin tumorigenesis in mice. On the other hand, SIRT6 acts as tumor suppressor in SCC by enhancing glycolysis in tumor propagating cells. Herein, pharmacological modulation of SIRT6 deacetylase activity was investigated in cSCC, with S6 (inhibitor) or MDL-800 (activator). In cSCC cells, S6 recreated the pro-differentiating effects of SIRT6 silencing, as the levels of Keratin 1, Keratin 10 and Loricrin were upregulated compared to controls. Next, the effects of SIRT6 pharmacological modulation were evaluated in a DMBA-TPA-induced skin cancer mouse model. Mice treated with the inhibitor S6 in a preventive approach, i.e. at the beginning of the promotion stage, presented reduced number and size of papillomas, compared to the controls. The epidermal hyperproliferation marker Keratin 6 and the cSCC marker Keratin 8 were less abundant when SIRT6 was inhibited. In S6-treated lesions, the Epithelial-Mesenchymal Transition (EMT) markers Zeb1 and Vimentin were less expressed compared to untreated lesions. In a therapeutic approach, i.e. treatment starting after papilloma appearance, the S6 group presented reduced papillomas (number and size), whereas MDL-800-treated mice displayed an opposite trend. In S6-treated lesions, Keratin 6 and Keratin 8 were less expressed, EMT was less advanced, with a higher E-cadherin/Vimentin ratio, indicating a delayed carcinogenesis when SIRT6 was inhibited. Our results confirm that SIRT6 plays a role in skin carcinogenesis and suggest SIRT6 pharmacological inhibition as a promising strategy in cSCC.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Papiloma / Neoplasias Cutâneas / Carcinoma de Células Escamosas / Sirtuínas Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Papiloma / Neoplasias Cutâneas / Carcinoma de Células Escamosas / Sirtuínas Idioma: En Ano de publicação: 2023 Tipo de documento: Article