Curcuminoids as Modulators of EMT in Invasive Cancers: A Review of Molecular Targets With the Contribution of Malignant Mesothelioma Studies

Our plain-English summary of Curcuminoids as Modulators of EMT in Invasive Cancers: A Review of Molecular Targets With the Contribution of Malignant Mesothelioma Studies, by D.L. Pouliquen, A. Boissard, C. Henry, et al (Frontiers in Pharmacology, 2022).

The study

• Authors: D.L. Pouliquen, A. Boissard, C. Henry, O. Coqueret, C. Guette
• Journal: Frontiers in Pharmacology
• Published: 2022;13:934534
• Type of article: Review
• Cited by: 11 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

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.

Copyright © 2022 Pouliquen, Boissard, Henry, Coqueret and Guette.

In plain English

This article was a review, not a new study. The authors searched PubMed, focusing on 2017 to 2022, for research on the epithelial-to-mesenchymal transition (EMT), a process linked to how cancers become invasive. They also looked at how curcumin and related compounds called curcuminoids act on EMT. Curcuminoids are mainly isolated from plants of the Curcuma genus or made as synthetic analogs. The authors summarized reports that these compounds act on many EMT-related signaling pathways. They then compared this literature with their own earlier experiments on malignant mesothelioma in rats. In one of those studies, rats carrying a highly invasive mesothelioma cell line (M5-T1) had more of two EMT-linked proteins, fibronectin and vimentin, in the liver than normal rats. This increase was completely reversed in curcumin-treated rats. Lower fibronectin and S100A4 levels in the spleen were among the markers of treatment effect in curcumin-treated rats. The authors concluded that curcuminoids have the potential to target multiple signaling pathways at once. They noted that primary targets still need to be told apart from downstream events. The article did not study asbestos exposure.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative literature review (PubMed search), with discussion of the authors' own earlier experimental rat mesothelioma studies
• Who was studied: Published research on EMT in cancer and on curcumin/curcuminoids, cross-checked against the term "malignant mesothelioma"; plus the authors' earlier experiments in rat models of malignant mesothelioma
• Exposure: Curcumin and curcuminoids (natural diarylheptanoids and synthetic curcumin analogs) as possible anti-cancer agents. No asbestos or fiber exposure was studied.
• Main results:
  • Across the reviewed literature, curcumin was reported to inhibit several pathways important for cancer stem cells, including NF-κB, PI3K/Akt/mTOR, Notch, Wnt and Hippo/YAP
  • In the authors' earlier rat study of liver colonization by the most invasive rat mesothelioma cell line (M5-T1), fibronectin and vimentin were more abundant than in normal rats, and this increase was completely reversed in curcumin-treated rats
  • In the same rat study, the S100 proteins encoded by S100a6 and S100a11 increased in untreated tumor-bearing rats, and this increase was completely reversed with curcumin. S100A4 showed only a tendency in the same direction.
  • In a later study of lymphoid organs from the same groups of rats, lower fibronectin and S100A4 levels in the spleen were among the biomarkers of therapeutic efficacy in curcumin-treated rats
  • In residual mesothelioma tumors, vimentin and IL-6 expression both decreased in curcumin-treated rats relative to untreated rats
  • Fibroblast growth factor 2 expression was highest in the most invasive rat tumor M5-T1, compared with the two less invasive tumors F5-T1 and F4-T2
• The authors' conclusion: The authors concluded that curcuminoids are of interest for research on EMT and cancer invasiveness because they can potentially act on multiple signaling pathways at the same time
• Limitations the authors state:
  • The authors stated that the primary molecular targets of curcuminoids still need to be distinguished from downstream events
  • The authors noted that signaling patterns and microenvironment composition may differ considerably by cancer location, histological subtype, and the grade and immune status of the host
  • The authors stated that the time- and dose-dependency of curcuminoid effects remains an unsolved question

Topics

Medical terms in this study, explained in our Lexicon: Mesothelioma, Metastasis, Tumor Microenvironment.

Related studies

• Curcumin Treatment Identifies Therapeutic Targets within Biomarkers of Liver Colonization by Highly Invasive Mesothelioma Cells-Potential Links with Sarcomas — D.L. Pouliquen, A. Boissard, et al. (2020)
• Lymphoid Organ Proteomes Identify Therapeutic Efficacy Biomarkers Following the Intracavitary Administration of Curcumin in a Highly Invasive Rat Model of Peritoneal Mesothelioma — D.L. Pouliquen, A. Boissard, et al. (2021)
• Proteomes of Residual Tumors in Curcumin-Treated Rats Reveal Changes in Microenvironment/Malignant Cell Crosstalk in a Highly Invasive Model of Mesothelioma — D.L. Pouliquen, M. Malloci, et al. (2022)
• Dysregulated Expression of the MicroRNA miR-137 and Its Target YBX1 Contribute to the Invasive Characteristics of Malignant Pleural Mesothelioma — T.G. Johnson, K. Schelch, et al. (2018)
• Molecular genetics and mechanisms of apoptosis in carcinomas of the lung and pleura: therapeutic targets — L.R. Motadi, N.L. Misso, et al. (2007)
• Molecular targets in malignant pleural mesothelioma treatment — G. Pasello, A. Favaretto (2009)

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