Background: Leukaemia is the most common form of blood cancer and includes a wide range of diseases characterized by uncontrolled growth of malignant haematopoietic cells (1). Since the chemical agents using in leukaemia treatment have a range of side effects, there is considerable interest in the potential of natural agents with lower side effects and greater compatibility with human physiology. Fucoidan, a natural marine polysaccharide, has shown promising inhibitory effect on various tumour cells (2)(3); however there are quite few studies on haematological malignancies. In this study, we examined fucoidan anticancer properties in different haematological malignancies subtypes.
Methods: To evaluate the anti-proliferative activity of fucoidan on haematological malignancies, different leukaemia cell lines were cultured with various concentrations of fucoidan. In vitro apoptosis assays WST-1 cytotoxicity assay, DNA content, Annexin V/PI staining and DNA fragmentation TUNEL assay were examined. We also measured activation of caspases 3, 8, 9 and cleavage of PARP to find out the mechanism of fucoidan-induced apoptosis.
Results: Our study showed that fucoidan inhibited the growth of acute promyelocytic leukaemia HL60 and NB4 cell lines in a time and dose dependent manner. Cell cycle and apoptosis studies revealed that sub G0/G1 population, DNA fragmentation and annexin V positive apoptotic cells increased in NB4 and HL-60 cell lines demonstrating that fucoidan has reduced their proliferation. Fucoidan also increased the level of activated caspase 3 , 8 and 9 as well as cleaved PARP in these cells.
Conclusion: Our data indicates that fucoidan has a selective inhibitory effect on acute promyelocytic leukaemia cell lines HL60 and NB4 while does not induce any such effect in chronic myelogenous leukaemia K562 and acute myeloblastic leukaemia KG1-a cell lines. Also, activation of both caspase 8 and 9 mediated by fucoidan demonstrates that it can activate apoptosis through both intrinsic and extrinsic pathways. These results suggest that fucoidan may prove useful in the development of treatment strategies in certain types of leukaemias.