Pouliquen Daniel L, Boissard Alice, Henry Cécile, Coqueret Olivier, Guette Catherine
Inserm, CNRS, Nantes Université, CRCI2NA, Université d'Angers, Angers, France.
ICO, Inserm, CNRS, Nantes Université, CRCI2NA, Université d'Angers, Angers, France.
Front Pharmacol. 2022 Jul 8;13:934534. doi: 10.3389/fphar.2022.934534. eCollection 2022.
Curcuminoids, which include natural acyclic diarylheptanoids and the synthetic analogs of curcumin, have considerable potential for fighting against all the characteristics of invasive cancers. The epithelial-to-mesenchymal transition (EMT) is a fundamental process for embryonic morphogenesis, however, the last decade has confirmed it orchestrates many features of cancer invasiveness, such as tumor cell stemness, metabolic rewiring, and drug resistance. A wealth of studies has revealed EMT in cancer is in fact driven by an increasing number of parameters, and thus understanding its complexity has now become a cornerstone for defining future therapeutic strategies dealing with cancer progression and metastasis. A specificity of curcuminoids is their ability to target multiple molecular targets, modulate several signaling pathways, modify tumor microenvironments and enhance the host's immune response. Although the effects of curcumin on these various parameters have been the subject of many reviews, the role of curcuminoids against EMT in the context of cancer have never been reviewed so far. This review first provides an updated overview of all EMT drivers, including signaling pathways, transcription factors, non-coding RNAs (ncRNAs) and tumor microenvironment components, with a special focus on the most recent findings. Secondly, for each of these drivers the effects of curcumin/curcuminoids on specific molecular targets are analyzed. Finally, we address some common findings observed between data reported in the literature and the results of investigations we conducted on experimental malignant mesothelioma, a model of invasive cancer representing a useful tool for studies on EMT and cancer.
姜黄素类化合物，包括天然无环二芳基庚烷类化合物和姜黄素的合成类似物，在对抗侵袭性癌症的所有特征方面具有相当大的潜力。上皮-间质转化（EMT）是胚胎形态发生的一个基本过程，然而，过去十年已经证实它参与了癌症侵袭的许多特征，如肿瘤细胞干性、代谢重编程和耐药性。大量研究表明，癌症中的EMT实际上是由越来越多的参数驱动的，因此了解其复杂性现在已成为定义未来应对癌症进展和转移的治疗策略的基石。姜黄素类化合物的一个特点是它们能够靶向多个分子靶点、调节多种信号通路、改变肿瘤微环境并增强宿主的免疫反应。尽管姜黄素对这些不同参数的影响已成为许多综述的主题，但迄今为止，尚未有关于姜黄素类化合物在癌症背景下对抗EMT作用的综述。本综述首先提供了所有EMT驱动因素的最新概述，包括信号通路、转录因子、非编码RNA（ncRNA）和肿瘤微环境成分，并特别关注最新发现。其次，针对这些驱动因素中的每一个，分析了姜黄素/姜黄素类化合物对特定分子靶点的影响。最后，我们讨论了文献报道的数据与我们对实验性恶性间皮瘤（一种侵袭性癌症模型，是研究EMT和癌症的有用工具）进行的研究结果之间观察到的一些共同发现。
