Fucoidan Induces Cell Aggregation and Apoptosis in Osteosarcoma MG-63 Cells

Abstract

Fucoidan, a sulfated polysaccharide found in brown algae, possesses various biological activities including anti-inflammatory and anti-cancer effects. In this study, we investigated the effects of fucoidan on the cell growth and morphology of human osteosarcoma MG-63 cells and found that fucoidan induces cell aggregation and apoptosis in osteosarcoma cells when the cells are treated with fucoidan upon seeding before becoming stably attached to the plates. Typical characteristics of apoptotic cells such as chromatin condensation and nuclear fragmentation were observed in fucoidan-treated cells. The number of annexin V-stained cells was increased by fucoidan treatment in a dose-dependent manner. Consistent with these results, cell viability and growth rate were decreased and cell spreading was inhibited in the presence of fucoidan, leading to rounded morphological changes of the cells. Our results demonstrate that fucoidan treatment results in cell aggregation through F-actin accumulation at the rounded cell cortex and apoptosis in osteosarcoma MG-63 cells.ARTICLE HISTORY

Fucoidan Inhibition of Osteosarcoma Cells is Species and Molecular Weight Dependent

“…Fucoidans from various different species of brown seaweed have been studied for anti-cancer applications. While most of the research revolves around more common forms of cancer, such as breast and colon cancer [6], use of fucoidan against osteosarcoma has recently been a keen area of interest [31][32][33], as even though it is a relatively less common cancer, the implications can be severe [34]. For the first time, here, we investigated the variable effects of crude fucoidan derived from two different species of brown algae, namely, F. vesiculosus (commercial source) and S. filipendula (derived from Colombian coast), and further evaluated the effect of different molecular weight fractions from 10-50 kDa (LMW), 50-100 kDa (MMW) and >100 kDa (HMW) fractions of fucoidan from S. filipendula on MG63 human osteosarcoma cells.…”

“…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].…”

“…The results showed that overall, HeLa 229 and A2780 cells were more strongly inhibited than HepG2 and LLC-PK1 cells, and even though the maximal sulphate content was found in the >100 kDa fraction, the cytotoxic activity was maximal for the 5-30 kDa fraction.Anti-tumor or anti-cancer activities of different fucoidans havebeen widely investigated for breast cancer [7,[21][22][23][24], colon/colorectal cancer [3,[25][26][27][28], liver cancer [13,29], lymphoma [8] and lung cancer [11,30]. However, the effect of fucoidan on osteosarcoma has only recently been investigated [31][32][33].Osteosarcoma is the most common type of bone cancer occurring in the proximal humerus (usually around the knee), distal femur and proximal tibia of younger children (more than 5 years of age), teenagers (it is the third most common cancer in adolescence) and older adults [34]. Currently, neoadjuvant and adjuvant chemotherapies, before and after surgery, are used for treating osteosarcoma.…”

“…Recently, it has been highlighted that cell proliferation, apoptosis, adhesion, invasion and metastasis represent potential biological targets for treating osteosarcoma [35], and that one of the most potent natural drugs for this application may be fucoidan. Fucoidanhas been shown to inhibit cancer cells by inducing apoptosis via several mechanisms [21,22,24,29,33,[36][37][38][39][40][41], such as inhibition of cell proliferation and invasion by targeting cell cycle proteins and the PI3K-Akt-mTOR pathway [42], inhibition of Vascular Endothelial Growth Factor and Matrix Metalloproteinases [30], enhancing ubiquitin-dependent TGFβ receptor degradation [23,43] and regulating the miR-29c/ADAM12 and miR-17-5p/PTEN axes [44].This study simultaneously compares the anti-cancer activities of crude fucoidans from two brown seaweed species F. vesiculosus and S. filipendula, and the effects of low-, medium-and high-MW (LMW, MMW and HMW) fractions of fucoidan derived from S. filipendula against MG63 osteosarcoma cells. Using size-fractionated fucoidan, we also demonstrate that as the molecular weight of fucoidan increases, the anti-cancer activity of fucoidan also increases.…”

“…Anti-tumor or anti-cancer activities of different fucoidans havebeen widely investigated for breast cancer [7,[21][22][23][24], colon/colorectal cancer [3,[25][26][27][28], liver cancer [13,29], lymphoma [8] and lung cancer [11,30]. However, the effect of fucoidan on osteosarcoma has only recently been investigated [31][32][33].…”