Fucoxanthin enhances 5-FU chemotherapeutic efficacy in colorectal cancer cells by affecting MMP-9 invasive proteins

ABSTRACT

Drug resistance is a major inconvenience which lowers the traditional chemotherapeutic efficacy and is a highly undesirable therapeutic problem which poses particular challenges in the case of colorectal cancer. Fucoxanthin is a natural orange-carotenoid, predominantly found in edible brown algae and justifiably considered as a nutritional ingredient with the capacity to powerfully enhance concurrent drug chemotherapy. It has been well-documented that fucoxanthin has good potential for anti-cancer activity while offering a remarkable range of biological activities. Accordingly, it has gained prominence in the research field as interest grows in the molecular mechanism which is associated with cancer therapy. This study was undertaken to assess the anti-cancer activity and to explore the molecular mechanism of fucoxanthin on the inhibition of cell proliferation, cell adhesion, and cell invasion, in addition to determining the synergistic effect of drug-drug combinative treatment in colorectal cancer cells. SW-620 cells were cultivated with fucoxanthin for 24, 48, 72, and 96 hours with co-treatment by 5-FU to evaluate the synergistic potential. The cell viability of cancerous cells was determined by MTT colorimetric assay. The inhibitory effects of cell invasion and adhesion were measured in the presence of fucoxanthin with 5-FU in various concentrations to determine MMP-9 gene and protein expression after treatment of the cells by RT-PCR and ELISA assay. The results illustrated that fucoxanthin profoundly inhibited cell proliferation of SW-620 cells, accompanied by arrested growth and diminished invasive ability, which was mediated at least in part by the down-regulation of MMP-9, mRNA, and protein expression. In particular, fucoxanthin strongly attenuated the anti-proliferative effect of established 5-FU by modulating the habitual hallmark of cancerous cells. These results illustrate the capacity of fucoxanthin to eradicate cancer cells and indicate the possibility that fucoxanthin could serve as a promising natural marine product derived from seaweed. The critical data in our studies will serve as the preliminary results for further studies of marine drugs in both experimental models and well-controlled clinical trials