Anandamide inhibits the Wnt/β-catenin signalling pathway in human breast cancer MDA MB 231 cells.

Abstract

We previously showed that methyl-F-anandamide, a stable analogue of the anandamide, inhibited the growth and the progression of cultured human breast cancer cells. As accumulating evidences indicate that the constitutive activation of the canonical Wnt pathway in human breast cancer may highlight a key role for aberrant activation of the β-catenin-TCF cascade and tumour progression, we studied the anandamide effect on the key elements of Wnt pathway in breast cancer cells. In this study we described that the treatment of human breast cancer cells, MDA MB 231 cells, with methyl-F-anandamide reduced protein levels of β-catenin in the cytoplasmic and nuclear fractions inhibiting the transcriptional activation of T Cell Factor (TCF) responsive element (marker for β-catenin signalling). The anandamide treatment resulted in up-regulation of epithelial markers, like E-cadherin with a concomitant decrease in protein levels of mesenchymal markers, including vimentin and Snail1. We, furthermore, observed that the induction of experimental epithelial-mesenchymal transition by exposure to adriamycin in MCF7 human breast cancer cell line was inhibited by anandamide treatment. In the present study we reported a novel anticancer effect of anandamide involving the inhibition of epithelial-mesenchymal transition, a process triggered during progression of cancer to invasive state.

• Authors: Chiara Laezza, Alba D'Alessandro, Simona Paladino, Anna Maria Malfitano, Maria Chiara Proto, Patrizia Gazzerro, Simona Pisanti, Antonietta Santoro, Elena Ciaglia, Maurizio Bifulco, Endocannabinoid Research Group
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 48 Issue 16 Pg. 3112-22 (Nov 2012) ISSN: 1879-0852 [Electronic] England
• PMID: 22425263 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical References

• 2-methyl-2'-F-anandamide
• Antibiotics, Antineoplastic
• Antigens, CD
• Antineoplastic Agents
• Biomarkers
• CDH1 protein, human
• CTNNB1 protein, human
• Cadherins
• Polyunsaturated Alkamides
• TCF Transcription Factors
• beta Catenin
• Doxorubicin

Topics

• Active Transport, Cell Nucleus
• Antibiotics, Antineoplastic (pharmacology)
• Antigens, CD
• Antineoplastic Agents (pharmacology)
• Biomarkers (metabolism)
• Breast Neoplasms (genetics, metabolism, pathology)
• Cadherins (genetics, metabolism)
• Doxorubicin (pharmacology)
• Epithelial-Mesenchymal Transition (drug effects)
• Female
• Genes, Reporter
• Humans
• MCF-7 Cells
• Polyunsaturated Alkamides (pharmacology)
• Promoter Regions, Genetic
• Protein Stability
• TCF Transcription Factors (genetics, metabolism)
• Time Factors
• Transfection
• Wnt Signaling Pathway (drug effects)
• beta Catenin (genetics, metabolism)