Docosahexaenoic acid-acylated phloridzin, a novel polyphenol fatty acid ester derivative, is cytotoxic to breast cancer cells.

Abstract

Docosahexaenoic acid-acylated phloridzin (PZ-DHA), a novel polyphenol fatty acid ester derivative, was synthesized through a regioselective acylation reaction with the aim of increasing the bioactivity of phloridzin (PZ) and docosahexaenoic acid (DHA). In this study, PZ-DHA's cytotoxic activity was explored using in vitro and in vivo models of mammary carcinoma. PZ-DHA was selectively cytotoxic for mammary carcinoma (MDA-MB-231, MDA-MB-468, 4T1, MCF-7 and T-47D) cells compared to non-malignant human mammary epithelial cells (HMEC and MCF-10A) and fibroblasts by MTS assay and Annexin-V-FLUOS/propidium iodide staining. Flow cytometric analysis of Oregon Green 488- and Ki-67-stained MDA-MB-231 cells showed antiproliferative activity of PZ-DHA at a subcytotoxic concentration. PZ-DHA also arrested MDA-MB-231 cell division at the G2/M phase and down-regulated expression of cyclin B1 and cyclin-dependent kinase 1 (CDK1). PZ-DHA-induced apoptosis in MDA-MB-231 cells was confirmed by caspase 3/7 activation in a luminescence assay and DNA fragmentation by TUNEL staining. Moreover, MDA-MB-231 xenograft growth in non-obese diabetic severe combined immunodeficient mice was suppressed by intra-tumoral administration of PZ-DHA. This study shows that PZ-DHA is selectively cytotoxic to breast cancer cells in vitro and in vivo, suggesting that further investigations of PZ-DHA are warranted as a potential treatment for breast cancer.

• Authors: Wasundara Fernando, Melanie R Power Coombs, David W Hoskin, H P Vasantha Rupasinghe
• Journal: Carcinogenesis (Carcinogenesis) Vol. 37 Issue 10 Pg. 1004-1013 (10 2016) ISSN: 1460-2180 [Electronic] England
• PMID: 27535497 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected].

Chemical References

• Cyclin B1
• Polyphenols
• Docosahexaenoic Acids
• Phlorhizin
• CDC2 Protein Kinase
• CDK1 protein, human
• Cyclin-Dependent Kinases

Topics

• Acylation (drug effects)
• Animals
• Apoptosis (drug effects)
• Breast Neoplasms (drug therapy, genetics, pathology)
• CDC2 Protein Kinase
• Cell Proliferation (drug effects)
• Cyclin B1 (biosynthesis, genetics)
• Cyclin-Dependent Kinases (biosynthesis, genetics)
• Docosahexaenoic Acids (administration & dosage)
• Female
• Humans
• MCF-7 Cells
• Mice
• Phlorhizin (administration & dosage, chemistry)
• Polyphenols (administration & dosage)
• Xenograft Model Antitumor Assays