title: 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.affiliation: Institute of Endocrinology and Experimental Oncology, IEOS CNR, Via Pansini 5, 80131 Naples, Italy. chilaez@hotmail.com
authors.forename: Chiara
authors.initials: C
authors.lastname: Laezza
authors.forename: Alba
authors.initials: A
authors.lastname: D'Alessandro
authors.forename: Simona
authors.initials: S
authors.lastname: Paladino
authors.forename: Anna
authors.initials: A
authors.lastname: Maria Malfitano
authors.forename: Maria
authors.initials: M
authors.lastname: Chiara Proto
authors.forename: Patrizia
authors.initials: P
authors.lastname: Gazzerro
authors.forename: Simona
authors.initials: S
authors.lastname: Pisanti
authors.forename: Antonietta
authors.initials: A
authors.lastname: Santoro
authors.forename: Elena
authors.initials: E
authors.lastname: Ciaglia
authors.forename: Maurizio
authors.initials: M
authors.lastname: Bifulco
mesh_terms: D021581:Active Transport, Cell Nucleus; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D015703:Antigens, CD; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005260:Female; D017930:Genes, Reporter; D006801:Humans; D061986:MCF-7 Cells; D053284:Polyunsaturated Alkamides / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D055550:Protein Stability; D051820:TCF Transcription Factors / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D060449:Wnt Signaling Pathway / Q000187:drug effects*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: C551918:2-methyl-2'-F-anandamide; D000903:Antibiotics, Antineoplastic; D015703:Antigens, CD; D000970:Antineoplastic Agents; D015415:Biomarkers; C513384:CDH1 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; D053284:Polyunsaturated Alkamides; D051820:TCF Transcription Factors; D051176:beta Catenin; D004317:Doxorubicin