Myelodysplastic syndrome is a medical condition that affects hematopoietic stem cells, which are responsible for generating red blood cells, white blood cells, and platelets. When these cells become abnormal, the body is no longer able to produce normal blood cells. A heterogeneous group of myeloid disorders characterized by peripheral cytopenia and increased risk of progression to acute myeloid leukemia (AML). There is a possibility that the levels of red blood cells, white blood cells, or platelets may decrease, or any combination of them may decrease. In certain cases, acute myeloid leukemia may develop and this can be attributed to prior chemotherapy treatment.

Given the potential risks involved, it is important to take steps to minimize them. With this in mind, I would like to share an essential study titled “Fucoidan inhibits proliferation of the SKM-1 acute myeloid leukemia cell line via the activation of apoptotic pathways and production of reactive oxygen species” by Chunmei Wet et al.

First, the study investigated the anticancer activity of fucoidan in the MDS/AML cell line SKM-1. It was observed that Fucoidan significantly inhibited the proliferation of SKM-1 cells at all concentrations ranging from 50 μg/ml to 500 μg/ml, as was determined by both Cell Counting Kit 8 assay and flow cytometry. At a fucoidan concentration of 50 μg/ml, the cell inhibition rate was 7.5±1.11% but increased to 43.4±2.72% at a concentration of 500 μg/ml. Furthermore, the inhibition rate increased by 9.2% when cells were exposed to 50 μg/ml fucoidan for 72 hours. (See Figure. 1) As a result, it was observed that the administration of fucoidan inhibited the proliferation of SKM-1 cells in a dose-dependent and time-dependent manner. This was determined to induce apoptosis and cause G1 arrest in the cell cycle.

The aim was to investigate whether fucoidan’s inhibitory effect on cell proliferation was the result of apoptotic cell death induction. To this end, SKM-1 cells treated with fucoidan (100 μg/ml) for 48 hours were analyzed using flow cytometry to measure the apoptotic rate. The apoptotic rate of SKM-1 cells after treatment with fucoidan (100 μg/ml) was 28.2±0.94% compared to 16.4±0.75% in controls. (See Figure-2) The study was further conducted by measuring the impact of fucoidan on the cell cycle of SKM-1 cells. After incubation with fucoidan (100 μg/ml) for 48 hours, cell cycle analysis was performed using flow cytometry. The G1/G0 population in the fucoidan-treated group was 47.71±1.23%, compared to 33.38±1.52% in the control group. Despite that, fucoidan treatment resulted in a decrease in the population of S-phase and G2/M-phase in contrast to the control group. The findings indicated that the administration of fucoidan elevated the apoptotic rate and resulted in cell cycle arrest at the G1/G0 phase.

Furthermore, to gain further insight into the mechanism of fucoidan-induced apoptosis in SKM-1 cells, RT-qPCR (transcription-quantitative polymerase chain reaction), and Western blot analysis were used to detect the expression of apoptosis-associated molecules Fas, caspase-8, caspase-9, and caspase-3 at the mRNA and protein levels, respectively. Gradual increase in the expression levels of the extrinsic pathway-associated molecules, Fas and caspase-8, and intrinsic pathway-associated molecule, caspase-9, was observed following treatment with fucoidan (100 μg/ml for 48 hours). In addition, the downstream effector caspase-3 was also activated. Activation of Caspase 9 was caused by the decrease in phosphoinositide 3 kinase/Akt signaling. This is indicated by a reduction in the levels of phosphorylated Akt, which suggests the involvement of the intrinsic apoptotic pathway. Fucoidan treatment of SKM-1 cells generated reactive oxygen species (ROS) as measured by staining with dichloro-dihydro-fluorescein diacetate. (See Figure. 3. The results suggest that the anti-cancer mechanism of fucoidan present in SKM-1 has a close association with the cellular cycle.

In conclusion, the reason behind the arrest and apoptotic cell death is partly due to the activation of apoptotic pathways and accumulation of intracellular ROS. According to the results, fucoidan can substantially inhibit the proliferation and induce apoptosis in SKM-1 cells, making them effective for the treatment of MDS. have demonstrated significant therapeutic potential.

Source: Mol Med Rep. 2015 Nov; 12(5): 6649–6655. doi 10.3892/mmr.2015.4252