PHLORIDZIN DOCOSAHEXAENOATE INDUCES CYTOTOXIC EFFECTS IN HUMAN LEUKEMIC CELLS
Date
2017-06-01T18:43:38Z
Authors
Arumuggam, Niroshaathevi
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
Polyphenols have potential as pharmacological adjuvants to overcome some clinical challenges that arise in leukemia management. The efficacy of polyphenols can be enhanced by acylation with fatty acids. In this study, the cytotoxic effects of docosahexaenoic acid-acylated phloridzin, known as phloridzin docosahexaenoate (PZ-DHA), was studied in two human leukemic cell lines, K562 and Jurkat cells. PZ-DHA significantly reduced the viability and ATP levels of the leukemic cells. PZ-DHA-induced cell morphological changes and apoptotic cell death was further studied by evaluating DNA fragmentation, lactate dehydrogenase (LDH) release, and caspase activation. PZ-DHA was also found to selectively kill Jurkat cells, while sparing normal murine T-cells. Furthermore, interferon-induced phosphorylation of STAT3 protein was downregulated in PZ-DHA-treated Jurkat cells. PZ-DHA also suppressed the proliferation of Jurkat cells xenotransplanted in zebrafish embryos. Both in vitro and in vivo findings from this study demonstrate the efficacy of PZ-DHA as a novel potential therapeutic agent for leukemia.
Description
Keywords
Phloridzin docosahexaenoate, flavonoid, leukemia, zebrafish, JAK/STAT pathway, Polyphenols