Malignant melanoma is one of the skin cancers caused by malignant melanocytes that make skin pigments. Melanoma develops drug resistance quickly and is highly malignant due to abnormalities in multiple proliferative signaling pathways. For example, in a few studies, epidermal growth factor receptor ERBB3 was abnormal in 70% of cases. There are four similar proteins in ERBB, and abnormalities have been observed in various cancer cells. Among them, in melanoma, the signal factor AKT is activated via ERBB3 and ERBB2, and it is understood that it leads to tumor progression.

Therefore, lapatinib, which is the target of action of ERBB2, is expected to be effective as a therapeutic drug for melanoma. However, side effects such as diarrhea and nausea can be therapeutic problems. Therefore, treatment strategies that enhance the drug’s effectiveness and alleviate the side effects are required. From this point of view, there is a need for a plan with high expectations for natural ingredients with anti-cancer effects. Among them, fucoidan, which is a sulfated polysaccharide contained in brown algae, has functions such as anti-inflammatory and anti-cancer effects and is attracting attention. In this blog, you will find the research content using fucoidan derived from New Zealand wakame seaweed in combination with lapatinib.

According to “The natural compound fucoidan from New Zealand Undaria pinnatifida synergizes with the ERBB inhibitor lapatinib enhancing melanoma growth inhibition” by Varsha Thakur et al.,  first, they cultured human melanoma WM266-4 cells in the coexistence of lapatinib and fucoidan. In addition, the cell viability was measured using the amount of energy (ATP) required for proliferation as a guideline to examine the combined effect of these cells. 

As a result, a decrease in fucoidan concentration-dependent ATP production was observed in the presence of lapatinib, demonstrating a synergistic growth-inhibitory effect (Fig. 1). Next, as a result of examining the expression level of the activated protein (p-ERBB3 / 2) to investigate the relationship with EFBB, a remarkable decrease in expression was observed in the presence of lapatinib unaided by fucoidan. The presentation of modified p-ART of downstream activity was entirely suppressed by the combined use of lapatinib and fucoidan (Fig. 2).

Finally, mice subcutaneously transplanted with WM266-4 cells were divided into four study groups: Control group (DMSO), Fucoidan alone administration group IFUCO), Lapatinib mono-administration group (LAP), and Fucoidan + lapatinib combination administration group (F + L). As a result of studying the changes in tumor volume and mouse body weight over three weeks, the almost complete suppression of tumor growth was observed in the fucoidan + lapatinib combination administration group (Fig. 3A).

While the results of mouse weight measurement showed that the single lapatinib administration group was observed about 10% of weight loss, no significant increase or decrease in mouse body weight was observed in the lapatinib + fucoidan combination administration group. This indicated that fucoidan worked well in reducing the side effects of lapatinib. (Fig. 3B).

Research results have also shown that fucoidan contributes to improving the pharmacological effects of lapatinib and reducing side effects. Its combination is helpful as a treatment for melanoma. It is expected that fucoidan will be used in combination for melanoma and other cancer treatments in the future.