Phloridzin docosahexaenoate, a novel fatty acid ester of a plant polyphenol, inhibits mammary carcinoma cell metastasis.
Cancer Lett
; 465: 68-81, 2019 Nov 28.
Article
in En
| MEDLINE
| ID: mdl-31473253
ABSTRACT
Triple-negative breast cancer (TNBC) tends to recur and metastasize following initial chemotherapy, which presents a treatment challenge. Here, we detail the anti-metastatic activity of phloridzin docosahexaenoate (PZ-DHA), synthesized from the natural polyphenol, phloridzin, and the ω-3 fatty acid, docosahexaenoic acid. Sub-cytotoxic PZ-DHA suppressed the migration of MDA-MB-231, SUM149, and 4T1 cells, as well as invasion by MDA-MB-231 and 4T1 cells. Sub-cytotoxic PZ-DHA also inhibited MDA-MB-231 expression of matrix metalloproteinase 2, and expression of epithelial-to-mesenchymal transition-associated transcription factors by MDA-MB-231 and SUM149â¯cells. Transforming growth factor-ß-induced Rho GTPase signaling in MDA-MB-231â¯cells and non-malignant MCF-10A mammary epithelial cells was suppressed by sub-cytotoxic PZ-DHA, which also inhibited Akt/phosphoinositide 3-kinase and extracellular signal-regulated kinase 1 and 2 signaling in MDA-MB-231â¯cells. Finally, intraperitoneal administration of PZ-DHA suppressed the metastasis of 4T1 and GFP-transfected MDA-MB-231â¯cells from the mammary fat pad to the lungs of BALB/c and NOD-SCID female mice, respectively, which was unrelated to any inhibition of primary tumor growth. There was no evidence of toxicity as PZ-DHA treatment did not affect liver or kidney function. We conclude that PZ-DHA might prevent or inhibit the progression of TNBC.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Phlorhizin
/
Docosahexaenoic Acids
/
Triple Negative Breast Neoplasms
/
Lung Neoplasms
Type of study:
Prognostic_studies
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
Cancer Lett
Year:
2019
Document type:
Article
Affiliation country: