Dipartimento di Scienze e Tecnologie, Università del Sannio, Via dei Mulini, 82100 Benevento, Italy.
Dipartimento di Scienze per gli Alimenti, la Nutrizione e l'Ambiente, Università degli Studi di Milano, Via Celoria 2, 20133 Milano, Italy.
Biomolecules. 2024 Aug 13;14(8):998. doi: 10.3390/biom14080998.
Several natural compounds have been found to act as PPARγ agonists, thus regulating numerous biological processes, including the metabolism of carbohydrates and lipids, cell proliferation and differentiation, angiogenesis, and inflammation. Recently, Cladosporols, secondary metabolites purified from the fungus , have been demonstrated to display an efficient ability to control cell proliferation in human colorectal and prostate cancer cells through a PPARγ-mediated modulation of gene expression. In addition, Cladosporols exhibited a strong anti-adipogenetic activity in 3T3-L1 murine preadipocytes, preventing their in vitro differentiation into mature adipocytes. These data interestingly point out that the interaction between Cladosporols and PPARγ, in the milieu of different cells or tissues, might generate a wide range of beneficial effects for the entire organism affected by diabetes, obesity, inflammation, and cancer. This review explores the molecular mechanisms by which the Cladosporol/PPARγ complex may simultaneously interfere with a dysregulated lipid metabolism and cancer promotion and progression, highlighting the potential therapeutic benefits of Cladosporols for human health.
几种天然化合物已被发现可作为 PPARγ 激动剂,从而调节许多生物过程,包括碳水化合物和脂质代谢、细胞增殖和分化、血管生成和炎症。最近,从真菌中分离得到的次级代谢产物 Cladosporols 已被证明能够通过 PPARγ 介导的基因表达调控有效控制人类结直肠和前列腺癌细胞的增殖。此外,Cladosporols 在 3T3-L1 小鼠前体脂肪细胞中表现出强烈的抗脂肪生成活性,防止其体外分化为成熟脂肪细胞。这些数据有趣地指出,Cladosporols 与 PPARγ 之间的相互作用,在不同细胞或组织的环境中,可能会对受糖尿病、肥胖、炎症和癌症影响的整个机体产生广泛的有益影响。本文综述了 Cladosporol/PPARγ 复合物可能同时干扰失调的脂质代谢和癌症促进和进展的分子机制,强调了 Cladosporols 对人类健康的潜在治疗益处。