Fucoidan enhances the therapeutic potential of arsenic trioxide and all-trans retinoic acid in acute promyelocytic leukemia, in vitro and in vivo
When the human APL cell line, NB4, was treated in vitro with fucoidan plus ATO and ATRA at therapeutic and sub-therapeutic doses, there was an increase in sub-G0/G1 cells, annexin V/PI-positive-apoptotic cells and DNA fragmentation. This reduction in proliferation and increase in apoptosis was accompanied by enhanced myeloid differentiation as indicated by an increased expression of CD11b. This was not observed with the AML cell line Kasumi-1, suggesting specificity for APL.
In vivo treatment of APL-bearing mice with fucoidan+ATRA or fucoidan+ATO delayed tumor growth, induced differentiation and increased tumor volume doubling time. The differentiated APL cells derived from the excised tumor mass exhibited decreased CD44 expression in fucoidan+ATRA treated mice. This could translate to decreased cell migration in APL patients.
Our findings provide evidence supporting the use of fucoidan as an adjuvant therapeutic agent in the treatment of APL.
History
Publication title
OncoTargetVolume
7Issue
29Pagination
46028-46041ISSN
1949-2553Department/School
Menzies Institute for Medical ResearchPublisher
Impact Journals LLCPlace of publication
United StatesRights statement
Copyright 2016 the authors. Licensed under Creative Commons Attribution Attribution 3.0 Unported (CC BY 3.0) https://creativecommons.org/licenses/by/3.0/Repository Status
- Open