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Proliferation and migration of PC-3 prostate cancer cells is counteracted by PPARγ-cladosporol binding-mediated apoptosis and a decreased lipid biosynthesis and accumulation.
Rapuano, Roberta; Riccio, Alessio; Mercuri, Antonella; Madera, Jessica Raffaella; Dallavalle, Sabrina; Moricca, Salvatore; Lupo, Angelo.
Afiliación
  • Rapuano R; Dipartimento di Scienze e Tecnologie, Università del Sannio, Via dei Mulini, 42, 82100 Benevento, Italy.
  • Riccio A; Dipartimento di Scienze e Tecnologie, Università del Sannio, Via dei Mulini, 42, 82100 Benevento, Italy.
  • Mercuri A; Dipartimento di Scienze e Tecnologie, Università del Sannio, Via dei Mulini, 42, 82100 Benevento, Italy.
  • Madera JR; Dipartimento di Scienze e Tecnologie, Università del Sannio, Via dei Mulini, 42, 82100 Benevento, Italy.
  • Dallavalle S; Dipartimento di Scienze per gli Alimenti, la Nutrizione e l'Ambiente, Università degli Studi di Milano, via Celoria 2, 20133 Milano, Italy.
  • Moricca S; Dipartimento di Scienze e Tecnologie Agrarie, Alimentari, Ambientali e Forestali (DAGRI), Università degli Studi di Firenze, Piazzale delle Cascine 28, 50144 Firenze, Italy.
  • Lupo A; Dipartimento di Scienze e Tecnologie, Università del Sannio, Via dei Mulini, 42, 82100 Benevento, Italy. Electronic address: lupo@unisannio.it.
Biochem Pharmacol ; 222: 116097, 2024 04.
Article en En | MEDLINE | ID: mdl-38428827
ABSTRACT

OBJECTIVES:

Chemoprevention, consisting of the administration of natural and/or synthetic compounds, appears to be an alternative way to common therapeutical approaches to preventing the occurrence of various cancers. Cladosporols, secondary metabolites from Cladosporium tenuissimum, showed a powerful ability in controlling human colon cancer cell proliferation through a peroxisome proliferator-activated receptor gamma (PPARγ)-mediated modulation of gene expression. Hence, we carried out experiments to verify the anticancer properties of cladosporols in human prostate cancer cells. Prostate cancer represents one of the most widespread tumors in which several risk factors play a role in determining its high mortality rate in men. MATERIALS AND

METHODS:

We assessed, by viability assays, PPARγ silencing and overexpression experiments and western blotting analysis, the anticancer properties of cladosporols in cancer prostate cell lines.

RESULTS:

Cladosporols A and B selectively inhibited the proliferation of human prostate PNT-1A, LNCaP and PC-3 cells and their most impactful antiproliferative ability towards PC-3 prostate cancer cells, was mediated by PPARγ modulation. Moreover, the anticancer ability of cladosporols implied a sustained apoptosis. Finally, cladosporols negatively regulated the expression of enzymes involved in the biosynthesis of fatty acids and cholesterol, thus enforcing the relationship between prostate cancer development and lipid metabolism dysregulation.

CONCLUSION:

This is the first work, to our knowledge, in which the role of cladosporols A and B was disclosed in prostate cancer cells. Importantly, the present study highlighted the potential of cladosporols as new therapeutical tools, which, interfering with cell proliferation and lipid pathway dysregulation, may control prostate cancer initiation and progression.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Próstata / PPAR gamma / Naftalenos Límite: Humans / Male Idioma: En Revista: Biochem Pharmacol Año: 2024 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Próstata / PPAR gamma / Naftalenos Límite: Humans / Male Idioma: En Revista: Biochem Pharmacol Año: 2024 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Reino Unido