Vergara Daniele, De Domenico Stefania, Tinelli Andrea, Stanca Eleonora, Del Mercato Loretta L, Giudetti Anna M, Simeone Pasquale, Guazzelli Nicola, Lessi Marco, Manzini Chiara, Santino Angelo, Bellina Fabio, Maffia Michele
Department of Biological and Environmental Sciences and Technologies, University of Salento, via Monteroni, Lecce, Italy.
Mol Biosyst. 2017 May 30;13(6):1131-1141. doi: 10.1039/c7mb00128b.
Resveratrol, a naturally occurring phytoalexin, has long been known to play an important regulatory role in key functions in cell physiology. This multifunctional role of resveratrol is explained by its ability to interact with several targets of various cell pathways. In the recent past, synthetic chemical modifications have been made in an attempt to enhance the biological effects of resveratrol, including its anti-cancer properties. In this study, we investigated the molecular mechanisms of action of novel trans-restricted analogues of resveratrol in which the C-C double bond of the natural derivative has been replaced by diaryl-substituted imidazole analogues. In ovarian cancer models, the results of in vitro screening revealed that the resveratrol analogues exhibited enhanced anti-proliferative properties compared with resveratrol. We found that the resveratrol analogues also significantly inhibited Akt and MAPK signalling and reduced the migration of IL-6 and EGF-treated cells. Finally, in ascite-derived cancer cells, we demonstrated that the resveratrol analogues reduced the expression of epithelial mesenchymal transition (EMT) markers. Collectively, these findings indicate the enhanced anti-cancer properties of the resveratrol analogues.
白藜芦醇是一种天然存在的植保素，长期以来人们已知它在细胞生理学的关键功能中发挥重要的调节作用。白藜芦醇的这种多功能作用可以通过其与各种细胞途径的多个靶点相互作用的能力来解释。最近，人们进行了合成化学修饰，试图增强白藜芦醇的生物学效应，包括其抗癌特性。在本研究中，我们研究了白藜芦醇新型反式受限类似物的作用分子机制，其中天然衍生物的碳 - 碳双键已被二芳基取代的咪唑类似物所取代。在卵巢癌模型中，体外筛选结果显示，与白藜芦醇相比，白藜芦醇类似物表现出更强的抗增殖特性。我们发现白藜芦醇类似物还显著抑制Akt和MAPK信号传导，并减少IL - 6和EGF处理细胞的迁移。最后，在腹水来源的癌细胞中，我们证明白藜芦醇类似物降低了上皮 - 间质转化（EMT）标志物的表达。总的来说，这些发现表明白藜芦醇类似物具有增强的抗癌特性。
