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Published on: October 27, 2020
Anthocyanidins inhibit epithelial-mesenchymal transition through a TGFβ/Smad2 signaling pathway in glioblastoma cells
Amira Ouanouki1, Sylvie Lamy1, Borhane Annabi1
1Laboratoire d'Oncologie Moléculaire, Centre de Recherche BioMed, Université du Québec à Montréal, Montréal, Québec, Canada.
Abstract:
Epidemiological studies have convincingly demonstrated that diets rich in fruits and vegetables play an important role in preventing cancer due to their polyphenol content. Among polyphenols, the anthocyanidins are known to possess anti-inflammatory, cardioprotective, anti-angiogenic, and anti-carcinogenic properties. Despite the well-known role of transforming growth factor-β (TGF-β) in high grade gliomas, the impact of anthocyanidins on TGF-β-induced epithelial-mesenchymal transition (EMT), a process that allows benign tumor cells to infiltrate surrounding tissues, remains poorly understood. The objective of this study is to investigate the impact of anthocyanidins such as cyanidin (Cy), delphinidin (Dp), malvidin (Mv), pelargonidin (Pg), and petunidin (Pt) on TGF-β-induced EMT and to determine the mechanism(s) underlying such action. Human U-87 glioblastoma (U-87 MG) cells were treated with anthocyanidins prior to, along with or following the addition of TGF-β. We found that anthocyanidins differently affected TGF-β-induced EMT, depending on the treatment conditions. Dp was the most potent EMT inhibitor through its inhibitory effect on the TGF-β Smad and non-Smad signaling pathways. These effects altered expression of the EMT mesenchymal markers fibronectin and Snail, as well as markedly reducing U-87 MG cell migration. Our study highlights a new action of anthocyanidins against EMT that supports their beneficial health and chemopreventive effects in dietary-based strategies against cancer. © 2016 Wiley Periodicals, Inc.
Insights
Anthocyanidins, particularly delphinidin, inhibit cancer cell invasion by blocking transforming growth factor-β (TGF-β)-induced epithelial-mesenchymal transition (EMT). This finding supports anthocyanins
Area of Science:
- Nutritional Biochemistry
- Cancer Biology
- Molecular Pharmacology
Background:
- Diets rich in fruits and vegetables are linked to cancer prevention due to polyphenol content.
- Anthocyanidins exhibit anti-inflammatory, cardioprotective, anti-angiogenic, and anti-carcinogenic properties.
- Transforming growth factor-β (TGF-β) is implicated in high-grade gliomas, promoting tumor cell invasion via epithelial-mesenchymal transition (EMT).
Purpose of the Study:
- To investigate the effects of specific anthocyanidins (cyanidin, delphinidin, malvidin, pelargonidin, petunidin) on TGF-β-induced EMT in glioblastoma cells.
- To elucidate the underlying molecular mechanisms of anthocyanidin action on EMT.
Main Methods:
- Human U-87 glioblastoma (U-87 MG) cells were treated with anthocyanidins.
- Cells were exposed to anthocyanidins prior to, concurrently with, or after TGF-β stimulation.
- Effects on EMT markers, signaling pathways (Smad and non-Smad), and cell migration were assessed.
Main Results:
- Anthocyanidins demonstrated differential effects on TGF-β-induced EMT based on treatment timing.
- Delphinidin (Dp) emerged as the most potent inhibitor of EMT.
- Dp inhibited TGF-β-mediated Smad and non-Smad signaling, reduced expression of fibronectin and Snail, and decreased U-87 MG cell migration.
Conclusions:
- Anthocyanidins, especially delphinidin, possess significant anti-EMT activity against glioblastoma cells.
- The inhibitory effects are mediated through modulation of TGF-β signaling pathways.
- These findings underscore the potential of anthocyanidins in dietary strategies for cancer chemoprevention.
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