Cannabidiol inhibits invasion and metastasis in colorectal cancer cells by reversing epithelial–mesenchymal transition through the Wnt/β-catenin signaling pathway

Abstract Colorectal cancer (CRC) is the leading cause of cancer deaths worldwide, wherein distant metastasis is the main reason for death. The non-psychoactive phytocannabinoid cannabidiol (CBD) effectively induces the apoptosis of CRC cells. We investigated the role of CBD in the migration and metastasis of CRC cells. CBD significantly inhibited proliferation, migration, and invasion of colon cancer cells in a dose- or time-dependent manner. CBD could also inhibit epithelial–mesenchymal transition (EMT) by upregulating epithelial markers such as E-cadherin and downregulating mesenchymal markers such as N-cadherin, Snail, Vimentin, and HIF-1α. CBD could suppress the activation of the Wnt/β-catenin signaling pathway, inhibit the expression of β-catenin target genes such as APC and CK1, and increase the expression of Axin1. Compared to the control group, the volume and weight of orthotopic xenograft tumors significantly decreased after the CBD treatment. The results demonstrated that CBD inhibits invasion and metastasis in CRC cells. This was the first study elucidating the underlying molecular mechanism of CBD in inhibiting EMT and metastasis via the Wnt/β-catenin signaling pathway in CRC cells. The molecular mechanism by which CBD inhibits EMT and metastasis of CRC cells was shown to be through the Wnt/β-catenin signaling pathway for the first time..

Medienart:

Artikel

Erscheinungsjahr:

2022

Erschienen:

2022

Enthalten in:

Zur Gesamtaufnahme - volume:149

Enthalten in:

Journal of cancer research and clinical oncology - 149(2022), 7 vom: 12. Aug., Seite 3587-3598

Sprache:

Englisch

Beteiligte Personen:

Feng, PanFeng [VerfasserIn]
Zhu, LongXun [VerfasserIn]
Jie, Jing [VerfasserIn]
Yang, PengXiang [VerfasserIn]
Sheng, Nan [VerfasserIn]
Chen, XiangFan [VerfasserIn]
Chen, Xia [VerfasserIn]

Links:

Volltext [lizenzpflichtig]

Themen:

Cannabidiol
Colorectal cancer
Epithelial–mesenchymal transition
Metastasis
Wnt/β-catenin signaling pathway

Anmerkungen:

© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2022. Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

doi:

10.1007/s00432-022-04265-x

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

OLC2144256551