Cladosporols A and B, two natural peroxisome proliferator-activated receptor gamma (PPARγ) agonists, inhibit adipogenesis in 3T3-L1 preadipocytes and cause a conditioned-culture-medium-dependent arrest of HT-29 cell proliferation,Biochimica et Biophysica Acta (BBA) - General Subjects

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Cladosporols A and B, two natural peroxisome proliferator-activated receptor gamma (PPARγ) agonists, inhibit adipogenesis in 3T3-L1 preadipocytes and cause a conditioned-culture-medium-dependent arrest of HT-29 cell proliferation
Biochimica et Biophysica Acta (BBA) - General Subjects ( IF 2.8 ) Pub Date : 2021-08-02 , DOI: 10.1016/j.bbagen.2021.129973
Roberta Rapuano ₁ , Pamela Ziccardi ₁ , Valentina Cioffi ₁ , Sabrina Dallavalle ₂ , Salvatore Moricca ₃ , Angelo Lupo ₁

Affiliation

Background

Obesity and type 2 diabetes mellitus, which are widespread throughout the world, require therapeutic interventions targeted to solve clinical problems (insulin resistance, hyperglycaemia, dyslipidaemia and steatosis). Several natural compounds are now part of the therapeutic repertoire developed to better manage these pathological conditions. Cladosporols, secondary metabolites from the fungus Cladosporium tenuissimum, have been characterised for their ability to control cell proliferation in human colon cancer cell lines through peroxisome proliferator-activated receptor gamma (PPARγ)-mediated modulation of gene expression. Here, we report data concerning the ability of cladosporols to regulate the differentiation of murine 3T3-L1 preadipocytes.

Methods

Cell counting and MTT assay were used for analysing cell proliferation. RT-PCR and Western blotting assays were performed to evaluate differentiation marker expression. Cell migration was analysed by wound-healing assay.

Results

We showed that cladosporol A and B inhibited the storage of lipids in 3T3-L1 mature adipocytes, while their administration did not affect the proliferative ability of preadipocytes. Moreover, both cladosporols downregulated mRNA and protein levels of early (C/EBPα and PPARγ) and late (aP2, LPL, FASN, GLUT-4, adiponectin and leptin) differentiation markers of adipogenesis. Finally, we found that proliferation and migration of HT-29 colorectal cancer cells were inhibited by conditioned medium from cladosporol-treated 3T3-L1 cells compared with the preadipocyte conditioned medium.

Conclusions

To our knowledge, this is the first report describing that cladosporols inhibit in vitro adipogenesis and through this inhibition may interfere with HT-29 cancer cell growth and migration.

General significance

Cladosporols are promising tools to inhibit concomitantly adipogenesis and control colon cancer initiation and progression.

中文翻译：

Cladosporols A 和 B，两种天然过氧化物酶体增殖物激活受体 γ (PPARγ) 激动剂，抑制 3T3-L1 前脂肪细胞的脂肪生成，并导致 HT-29 细胞增殖的条件培养基依赖性停滞

背景

肥胖症和 2 型糖尿病在世界范围内普遍存在，需要针对临床问题（胰岛素抵抗、高血糖、血脂异常和脂肪变性）进行治疗干预。几种天然化合物现在是为更好地管理这些病理状况而开发的治疗方案的一部分。Cladosporols 是来自真菌Cladosporium tenuissimum 的次生代谢物，其特征在于它们能够通过过氧化物酶体增殖物激活受体 γ (PPARγ) 介导的基因表达调节来控制人结肠癌细胞系中的细胞增殖。在这里，我们报告了有关枝孢菌素调节小鼠 3T3-L1 前脂肪细胞分化能力的数据。

方法

细胞计数和MTT测定用于分析细胞增殖。进行 RT-PCR 和蛋白质印迹分析以评估分化标记物的表达。通过伤口愈合试验分析细胞迁移。

结果

我们表明，cladosporol A 和 B 抑制了 3T3-L1 成熟脂肪细胞中脂质的储存，而它们的给药不影响前脂肪细胞的增殖能力。此外，两种枝孢菌素都下调了脂肪生成的早期（C/EBPα 和 PPARγ）和晚期（aP2、LPL、FASN、GLUT-4、脂联素和瘦素）分化标志物的 mRNA 和蛋白质水平。最后，我们发现与前脂肪细胞条件培养基相比，来自枝孢菌素处理的 3T3-L1 细胞的条件培养基抑制了 HT-29 结肠直肠癌细胞的增殖和迁移。