<p>The Natural Product Fucoidan Inhibits Proliferation and Induces Apoptosis of Human Ovarian Cancer Cells: Focus on the PI3K/Akt Signaling Pathway</p>

Abstract

Objective: Ovarian cancer (OC) is the leading cause of death among gynecological tumors; however, no effective treatment is currently available. Fucoidan, which is extracted from marine algae, has significant anti-cancer effects. The aim of this study was to determine the effects of fucoidan on the proliferation and apoptosis of OC cells through inhibition of the PI3K/Akt signaling pathway. Methods: Human ovarian normal epithelial cells (IOSE80) and human OC cells (SKOV-3, A2780, OVCAR-3, TOV-112D, and Caov-3) were selected to verify the safety of fucoidan at various doses in SKOV-3 and Caov-3 cells as well as a xenograft mouse model using various molecular biology techniques. Results: Fucoidan had no significant effect on normal ovarian epithelial cells, but had significantly inhibited the proliferation of OC cells, induced cell cycle arrest at the G0/G1 phase, increased the proportion of apoptotic cells and expression of pro-apoptotic proteins, and inhibited the expression of PI3K and phosphorylation of Akt, which could be partly rescued by IGF-1. Conclusion: Fucoidan had anti-tumor effects both in vivo and in vitro via a mechanism that is related to the inhibition of the PI3K/Akt signaling pathway.

Anticancer Activity of Fucoidan via Apoptosis and Cell Cycle Arrest on Cholangiocarcinoma Cell

“…In the acute promyelocytic leukemia cell line incubated with fucoidan resulted in cell cycle arrest in the G1 phase (Atashrazm et al, 2016). The same trend of the result was also demonstrated in HT29 colorectal cancer cells, MCF-7 breast cancer cells, and human ovarian cancer cells with downregulation of cyclin D1 and CDK4 (Banafa et al, 2013;Han et al, 2015;Liu et al, 2020). In the present study, we found that treatment with fucoidan in CL-6 cells resulted in cell cycle arrest in the G0/G1 phase.…”

“…Furthermore, Western blot analysis revealed the decreased expression levels of cyclin D1 and CDK4. The suppression of the PI3K/Akt signaling pathway by fucoidan results in the decreased expression levels of cyclin D1 and CDK4 which induce cell cycle arrest in the G0/G1 phase as described by a recent study (Liu et al, 2020) In conclusion, the results presented in this study revealed that fucoidan could exert cytotoxicity in CL-6 cholangiocarcinoma via the induction of apoptosis and cell cycle arrest. Nevertheless, future research about the anticancer effect of fucoidan against cholangiocarcinoma should be investigated in other signaling pathways related to its critical characteristics such as migration, invasion, and angiogenesis.…”

“…These polysaccharides are used for various purposes especially in the food-processing industry, medicine, and biotechnology (Giavasis, 2014). Several previous studies suggested that fucoidan exerts the growth and proliferation inhibition in human cancer cells via apoptotic induction (Bai et al, 2020;Blaszczak et al, 2018;Chantree et al, 2020;Deepika et al, 2019;He et al, 2019;Liu et al, 2020;Narayani et al, 2019;Palanisamy et al, 2018). Moreover, some studies reported the effect of fucoidan in suppressing the invasion (Lin et al, 2017) and metastasis (Alekseyenko et al, 2007) of cancer cells.…”

The Therapeutic Potential of the Anticancer Activity of Fucoidan: Current Advances and Hurdles

“…At a concentration of 1.0 mg/mL, fucoidan derived from C. okamuranus increased the G0/G1-phase population fraction of Huh7 hepatocarcinoma cells. This mechanism was followed by a decrease in the S-phase fraction, suggesting that fucoidan may cause cell cycle arrest in the G0/G1 phase [ 53 ]. Zhang et al demonstrated that when high-molecular-weight fucoidan was extracted from Cladosiphon novae-caledoniae kylin and then digested with glysidases, it produced LMWF.…”

Fucoidan Inhibits the Progression of Hepatocellular Carcinoma via Causing lncRNA LINC00261 Overexpression

“…As a natural polysaccharide extracted from brown algae, fucoidan was proved to have many biological effects (12)(13)(14)(15)(16). The anti-tumor abilities of fucoidan were confirmed in pancreatic cancer, bladder cancer, ovarian cancer and other types of cancers (65)(66)(67)(68). Fucoidan could inhibit the occurrence and development of tumor by regulating tumor immunity (21,22), inhibiting angiogenesis (23), interfering with cell cycle and apoptosis (19,20), which is considered to have a broad prospect in the field of tumor therapy.…”