Fucoidan Derived from Fucus vesiculosus Inhibits the Development of Human Ovarian Cancer via the Disturbance of Calcium Homeostasis, Endoplasmic Reticulum Stress, and Angiogenesis

• Published in: Marine drugs Vol. 18; no. 1; p. 45
• Main Authors: Bae, Hyocheol, Lee, Jin-Young, Yang, Changwon, Song, Gwonhwa, Lim, Whasun
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 09.01.2020; MDPI
• Subjects: 1-Phosphatidylinositol 3-kinase; Angiogenesis; Animals; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Apoptosis; Calcium; Calcium (mitochondrial); Calcium (reticular); Calcium - metabolism; Calcium homeostasis; Cancer; Cardiotoxicity; Cell cycle; Cell growth; Cell Line, Tumor; Cell proliferation; Cell Proliferation - drug effects; Cells; Cytochrome; Cytochrome c; Cytochromes; Danio rerio; Drug resistance; Endoplasmic reticulum; Endoplasmic Reticulum - drug effects; Female; Flow cytometry; Freshwater fishes; Fucoidan; Fucus - chemistry; Fucus vesiculosus; Homeostasis; Homeostasis - drug effects; Humans; Inactivation; Kinases; Kinesis; Larvae; MAP kinase; marine drug; Marine organisms; Mitochondria; Neoplasms; Neovascularization, Pathologic - prevention & control; Ovarian cancer; Ovarian Neoplasms - drug therapy; Ovaries; Pharmaceuticals; Phosphorylation; Polysaccharides - pharmacology; Polysaccharides - toxicity; Proliferation; Proteins; Reactive oxygen species; Signal transduction; Stress, Physiological - drug effects; Toxicity; Toxicity Tests; Xenografts; Xenotransplantation; Zebrafish; calcium homeostasis; ovarian cancer; fucoidan; angiogenesis; marine drug
• ISSN: 1660-3397; 1660-3397
• DOI: 10.3390/md18010045

Marine organisms are sources of several natural compounds with potential clinical use. However, only a few marine-based pharmaceuticals have been approved for use due to limited knowledge on their biological activities. Here, we identified the functional role of fucoidan extracted from on ovarian cancer. Fucoidan increased the death of ES-2 and OV-90 cells, through a reduction in proliferation, cell cycle arrest, releases of cytochrome c, reactive oxygen species (ROS) generation, and endoplasmic reticulum (ER) stress. Additionally, fucoidan increased the concentration of cytosolic and mitochondrial calcium in both cells. The decrease of cell proliferation was controlled by the inactivation of PI3K and MAPK signaling cascades in ES-2 and OV-90 cells. In a toxicity assay with normal zebrafish larvae, fucoidan did not induce toxicity, cardiotoxicity, development, kinesis, and apoptosis at different concentrations. However, it disrupted tumor formation and vascular development in a zebrafish xenograft model and angiogenesis transgenic (Tg, fli1-eGFP) model, respectively. Collectively, the results indicate that fucoidan may be a novel pharmaceutical for the management of human ovarian cancer.