Fucoidan Inhibits the Proliferation of Leiomyoma Cells and Decreases Extracellular Matrix-Associated Protein Expression

Abstract

Background/Aims: Uterine leiomyomas (ULs) are benign uterine tumors, and the most notable pathophysiologic feature of ULs is excessive accumulation of extracellular matrix (ECM). Fucoidan is a polysaccharide extracted from brown seaweeds that has a wide range of pharmacological properties, including anti-fibrotic effects. We aimed to study the effect of fucoidan on the growth of ULs activated by transforming growth factor beta (TGFβ). Methods: We used ELT-3 (Eker rat leiomyoma tumor-derived cells) and HUtSMC (human uterine smooth muscle cells) as in vitro models. Cell viability was determined by the MTT assay. Cell colony formation was stained using crystal violet. The side population, cell cycle and apoptosis were analyzed using flow cytometry. Protein expression was assayed by western blot analysis. We also conducted in vivo experiments to confirm the inhibitory effects of fucoidan in nude mouse xenograft models. Tumor tissues were assayed by immunohistochemistry analysis. Results: In our study, fucoidan caused a 50% growth inhibition using a dose of 0.5 mg/ml and decreased the stem cell activity after 48 h. In addition, fucoidan induced sub-G1 cell cycle arrest and apoptosis. Fucoidan down-regulated fibronectin, vimentin, α-SMA and the COL1A1 protein levels in TGFβ3-induced ELT-3 cells. In the cellular mechanism, fucoidan abrogated TGFβ3-induced levels of p-Smad2 and p-ERK1/2, as well as β-catenin translocation into the nucleus. Furthermore, fucoidan suppressed xenograft tumor growth in vivo. Conclusion: Fucoidan displays anti-proliferation and anti-fibrotic effects and exerts protective effects against ULs development.

Preventive Effects of Fucoidan and Fucoxanthin on Hyperuricemic Rats Induced by Potassium Oxonate

“…Hi-Q oligo-fucoidans (Fc) and high-stability fucoxanthin (HS Fucoxanthin, HSFUCO) (Fx) were derived from Laminaria japonica and obtained from Hi-Q Marine Biotech International Ltd. (New Taipei City, Taiwan) [27]. Oxonic acid (potassium salt), hypoxanthine, and the xanthine oxidase fluorometric assay kit were purchased from Cayman Chemical (Ann Arbor, MI, USA).…”

Fucoidan Inhibition of Osteosarcoma Cells is Species and Molecular Weight Dependent

“…Indeed, several studies (reviewed in Reference [60]) claim that fucoidans, mainly from F. vesiculosus or U. pinnatifida, induce apoptosis via inhibition of phosphatidylinositol 3-kinase (PI3K)/Akt in human acute promyelocytic leukaemia (APL) cells [48] and PC-3 prostate cancer cells [38], via inhibition of the mitogen-activated protein kinase (MAPK) pathway in AML cells [48], MC3 human mucoepidermoid carcinoma cells [61] and DU-145 Prostate Cancer Cells [62], via downregulation of ID-1 (expressed in actively proliferating cells) in hepatocellular carcinoma cells [63], via downregulation of β-catenin in Eker rat leiomyoma tumour-derived cells [64] and PC-3 cells [38], and via generation of reactive oxygen species (ROS) in 5637 human bladder cancer cells [65], human hepatocellular carcinoma SMMC-7721 cells [59] and MCF-7 breast cancer cells [22,66]. Recently, commercial fucoidan from U. pinnatifida (average 130 kDa with 21% ± 3% fucose, 20% ± 5% galactose, 2% ± 2% mannose, and 30% ± 3% sulphate) was also shown to induce apoptosis in MG63 osteosarcoma cells characterised by increased roundness of the cells due to accumulation of F-actin at the cortex and increased expression of Annexin V together with chromatin condensation [33].…”

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

“…Fucoidan has extensive physiological activities such as anti-coagulant [10], antioxidant [11], immuno-modulatory [12], anti-inflammatory [13], anti-bacterial activity [14], and anti-obesity [15,16] properties. Additionally, many studies suggest that fucoidan has an anti-cancer effect in various cancer cells such as leiomyosarcoma [17], bladder cancer [18], mastocarcinoma [19], colorectal cancer [20], and hepatocellular carcinoma [21]. There are several studies confirming the effects of fucoidan in ovarian cancer.…”