Ovarian, uterine, and cervical cancers are one of the most common malignancies that adversely affect the female genitals. Although the rate of ovarian cancer is lower than the other two, early clinical diagnosis remains challenging and often delayed. 70% of patients with ovarian cancer have infiltration of peripheral tissue at diagnosis, which increases the risk of death. So, these results in the highest case fatality rate among all gynecologic tumors of ovarian cancer.

Fucoidan is a marine algae extracted from a high molecular weight polysaccharide and has many biological functions such as action, anti-inflammatory action, antioxidant action, and regulation of glucose metabolism. However, the assessment of ovarian cancer (OC) is currently unclear on the Fucoidan’s effect. According to “The study, The Natural Fucoidan Inhibits Proliferation and Induces Apoptosis of Human Ovarian Cancer Cells: Focus the PI3K/Akt Signaling Pathway,” by Shuhab Liu et al., they evaluated the anticancer effect of Fucoidan on ovarian cancer. Researchers conducted an in-depth investigation of the mechanism of fucoidan inhibitory action via the PI3K / Akt signaling pathway, which may involve the inhibitory impact on other cancers.

First, researchers verified the inhibitory effect of Fucoidan on OC cells in the study. Following that, treated normal ovarian epithelial cells (IOSE80) and OC cells (SKOV-3, A2780, OVCAR-3, TOV-112D, and Caov-3) with various concentrations of fucoidan (0-150 μg / mL) Did. Cell proliferation was measured at various time points (0-72 hours). The results showed that Fucoidan could effectively inhibit OC cell proliferation in a concentration and time-dependent manner but had little effect on normal epithelial cells.

Next, researchers examined at what stage of the proliferative cell cycle of OC cells that Fucoidan was inhibited. Western blot analysis showed that Fucoidan significantly reduced CDK-4, CDK-6, cyclin-E, cyclin-D1, E2F-1, and pRb and showed increased protein expression cyclin-dependent kinase inhibitors p21 and p27. From this, it is considered that Fucoidan mainly induces cell cycle arrest by G0 / G1 phase arrest.

And researchers verified the Fucoidan mechanism of action of apoptosis. Two OC cell lines, SKOV-3 and Caov-3, were treated with different concentrations of Fucoidan for 48 hours and then tested for protein expression.

It was proved that the expression level of activated caspase enzyme was significantly higher in fucoidan-treated OC cells than that in the control group. In contrast, the expression level of the anti-apoptotic protein Bcl-2 was decreased. Moreover, the addition of 50 μM Z-VAD-FMK (a permeable and irreversible pan-caspase inhibitor) 1 hour before fucoidan (100 μg / mL) administration significantly reduced the number of apoptotic cells. These results indicate that Fucoidan can effectively promote mitochondrial apoptosis in OC cells via a caspase-dependent pathway.

Then, they investigated the association with PI3K, which induces phosphorylation of Akt and regulates cell function. Results Treatment with 100 μg / mL of Fucoidan significantly reduced phosphorylated Akt and PI3K expression (Fig. 1). Therefore, it was observed that Fucoidan presented an antitumor effect via the PI3K / Akt pathway. Finally, we examined the tumor growth inhibitory effect in vivo using mice that were subcutaneously injected with SKOV3. As a result, the tumor size and weight of the fucoidan-administered group were significantly reduced compared to those of the control group (Fig2). The clinical application of Fucoidan may positively represent a potential drug for the treatment of ovarian cancer.

             Fig1)     Control         Fu       IGF-1       Fu+IGF-1           Control        Fu              IGF-1          Fu+IGF-1