Abstract
The morbidity and mortality associated with current therapies for acute promyelocytic leukemia (APL) remain a significant clinical concern, despite improvements in patient survival. Consequently, the development of adjuvant therapies that increase efficacy while reducing morbidities is important. Reducing the concentration of the toxic drugs in adjuvant therapy has the potential to reduce unwanted side effects. Therefore, this study aimed to determine the synergistic effects of fucoidan, an anti-tumor agent, with current APL therapies.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.
Highlights
Fucoidan, a natural substance derived from marine algae, has immunomodulatory and cytotoxic activities and has been investigated as a potential anti-cancer agent [1, 2]
The acute promyelocytic leukemia NB4 cell line was treated with 20 μg/ml fucoidan and increasing concentrations of arsenic trioxide (ATO) for 48 hours and cell proliferation was assessed
To examine whether the ATO activity observed was specific to acute promyelocytic leukemia (APL) cells, the Kasumi-1 acute myeloid leukemia (AML) cell line was treated with ATO and fucoidan
Summary
A natural substance derived from marine algae, has immunomodulatory and cytotoxic activities and has been investigated as a potential anti-cancer agent [1, 2]. The cytotoxic and immunomodulatory effects have led to the proposal of fucoidan as a putative adjuvant therapy in combination with standard therapies. Synergistic effects of fucoidan with standard anti-cancer components have been reported. Administration of oral fucoidan combined with standard chemotherapy, significantly decreased general fatigue in patients with colorectal cancer compared to those who only received standard chemotherapy. Mechanisms underlying the anti-cancer activity of fucoidan, as well as other information such as route and dose of administration, and its side effects have been previously reviewed [7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
