EFFICACY AND SAFETY OF DOCOSAHEXAENOIC ACID ACYLATED PHLORIDZIN FOR TREATING TRIPLE NEGATIVE BREAST CANCER

Abstract

Phloridzin (PZ), a polyphenol compound found in apple, exerts glucose transporter inhibitory and estrogen-like effects. Therapeutic applications of PZ are limited due to its poor bioavailability. In this study, anitiproliferative efficacy of docosahexaenoic acid (DHA) acylated PZ (PZ-DHA) was investigated using a triple negative breast cancer cell line (MDA-MB-231). PZ-DHA, but not PZ, caused the death of MDA-MB-231 in vitro which was both time- and dose-dependent. PZ-DHA-induced apoptosis was indicated by DNA fragmentation and activation of caspase 3/7. However, reactive oxygen species production was not required for PZ-DHA-mediated cell death. PZ-DHA showed low cytotoxicity toward human mammary epithelial cells. Moreover, in vivo tumor suppresser effect of PZ-DHA was observed when MDA-MB-231 cells xenografted non-obese diabetic severe combined immune-deficient (NOD-SCID) mice were subjected to intratumoral injections of PZ-DHA. Anticancer efficacy observed in cell cultures and mice warrant further investigations of PZ-DHA as a potential treatment for breast cancer.