Fucoidan Fucoidan Research Health Benefit of Fucoidan

Growth inhibitory effect of fucoidan on oral cancer

September 26, 2022

Oral cancer is one of the most common head and neck cancers. However, the frequency of occurrence is about 1 to 3% of all cancers, which is not very high. Unlike other cancers,  early detection is easy in such types of cancers because the affected area can be seen directly. Sadly, people hardly notice or ignore it. Hence, many cases are left untreated until it progresses, and the number of deaths from cancer is increasing rapidly.

 detect oral cancer

In addition to surgical resection, chemotherapy and radiotherapy are effective treatments. However, it causes severe adverse effects to accompany them on the body with existing symptoms, which is a problem. Therefore, developing anticancer agents with antiproliferative effects that are selective for cancer cells and have minimal side effects on normal cells is expected.

On a positive note, seaweed is a wonderful supplement, does not contain cytotoxic, and is well known as a highly nutritious and functional food. Fucoidan is an active polysaccharide extracted from brown algae such as Fucus vasiculosus, kelp, and wakame and has been proven to have various physiological activities in previous studies.

Hence, in this blog, I would like to introduce the research “Brown algae-derived fucoidan exerts oxidative stress-dependent antiproliferation on oral cancer cells,” which focuses on the selective antiproliferative ability of fucoidan against oral cancer. This study verified the apoptosis-inducing action, oxidative stress action, and DNA damage action of fucoidan.

Firstly, to verify the cancer-selective antiproliferative effects of fucoidan, oral cancer cells (Ca9-22, CAL27, OC-2, HSC-3, and OECM-1) and non-malignant oral cells (S-G) were treated with 800 ~1200 µg/mL fucoidan in medium supplemented was measured cell viability 48 hours after culture. As a result, the viability of the normal cells, S-G, was kept high. In contrast, the viability of the oral cancer cell line decreased significantly depending on the fucoidan concentration (Fig. 1, ).

In addition, treatment of the antioxidant NAC with fucoidan weakened the antiproliferative effect (Fig. 1, right), suggesting that selective oxidative stress on oral cancer cells is involved in the anticancer effect.

So, to clarify the mechanism of fucoidan’s anticancer effect, they examined its impact on the cell cycle. Oral cancer cells treated with fucoidan had a higher proportion of cells in the subG1 phase and fewer cells in the S2/M phase than untreated cells, but in S-G cells, virtually no effect was observed on subG1 and S2/M phase cell numbers. On the other hand,  in S-G cells, almost no effect was observed on subG1 and S2/M phase cell numbers.

Furthermore, NAC treatment suppressed the fucoidan-induced increase in subG1 cells. Later, they used annexin V, which detects apoptosis, to verify the apoptosis-inducing effect of fucoidan on oral cancer cells. Fucoidan increased apoptosis in Ca9-22 and CAL27 cells more than in S-G cells, and NAC attenuated the effect.

Additionally, as a result of examining the effect on caspase 3, 8, and 9 signaling that induces apoptosis, fucoidan showed a more substantial activation effect in Ca9-22 cells and CAL cells than in S-G cells. NAC treatment also attenuates this effect, indicating that oxidative stress induced by fucoidan treatment is required for caspase activation and apoptosis induction.

Finally, to verify the oxidative damage of DNA, we examined the expression status of marker proteins such as γH2AX and 8-OHdG. As a result, both markers increased in Ca9-22 and CAL27 cells treated with fucoidan but not in S-G cells. NAC also attenuated the effect (Fig. 2). From this study, fucoidan induces oxidative stress and DNA damage without impairing the antioxidant mechanism in oral cancer cells. Also, it induces apoptosis accompanied by abnormal cell cycle progression, thereby inhibiting the growth of oral cancer cells was shown to exhibit. At the same time, fucoidan showed hardly effect on non-malignant cells, so it is expected that fucoidan will be applied as a therapeutic agent for oral cancer with few side effects.

Fig.1) Viability of fucoidan-supplemented oral cancer cells and normal cells
Fig. 2) Increase in DNA damage markers by fucoidan