Fucoidan Does Not Exert Anti-Tumorigenic Effects on Uveal Melanoma Cell Lines

Abstract

Background. The polysaccharide fucoidan is widely investigated as an anti-cancer agent. Here, we tested the effect of fucoidan on uveal melanoma cell lines. Methods. The effect of 100 µM fucoidan was investigated on five cell lines (92.1, Mel270 OMM1, OMM2.3, OMM2.5) and of 1 µg/mL–1 mg/mL fucoidan in two cell lines (OMM1, OMM2.3). Cell proliferation and viability were investigated with a WST-1 assay, migration in a wound healing (scratch) assay. Vascular Endothelial Growth Factor (VEGF) was measured in ELISA. Angiogenesis was evaluated in co-cultures with endothelial cells. Cell toxicity was induced by hydrogen-peroxide. Protein expression (Akt, ERK1/2, Bcl-2, Bax) was investigated in Western blot. Results. Fucoidan increased proliferation in two and reduced it in one cell line. Migration was reduced in three cell lines. The effect of fucoidan on VEGF was cell type and concentration dependent. In endothelial co-culture with 92.1, fucoidan significantly increased tubular structures. Moreover, fucoidan significantly protected all tested uveal melanoma cell lines from hydrogen-peroxide induced cell death. Under oxidative stress, fucoidan did not alter the expression of Bcl-2, Bax or ERK1/2, while inducing Akt expression in 92.1 cells but not in any other cell line. Conclusion. Fucoidan did not show anti-tumorigenic effects but displayed protective and pro-angiogenic properties, rendering fucoidan unsuitable as a potential new drug for the treatment of uveal melanoma.

Effects of a Newly Developed Enzyme-Assisted Extraction Method on the Biological Activities of Fucoidans in Ocular Cells

“…Oxidative stress in the uveal melanoma cell line OMM-1 was induced by treatment with 1 mM H 2 O 2 as previously shown [39]. The appropriate H 2 O 2 concentration to lower cell viability of OMM-1 cells to nearly 50% after 24 h was previously determined [19] and applied for the assessment of protective effects of fucoidans (1, 10, 50 and 100 µg/mL).…”

Fucoidan Immobilized at the Surface of a Fibrous Mesh Presents Toxic Effects over Melanoma Cells, But Not over Noncancer Skin Cells

“…22−24 However, due its natural origin and intrinsic variability, not all fucoidan extracts may present this antitumor behavior. 7,27,34 Herein, as a first screening, fucoidan cytotoxicity and antitumor capability was tested in its soluble form. After this validation and trying to diminish the potential side effects of systemic therapies, an alternative and innovative therapeutic strategy is proposed by incorporating fucoidan on an electrospun nanofibrous mesh, aiming to act as a skin patch able to be easily and locally applied at the tumor site.…”

“…7,26 In fact, despite the previous reports on the cytotoxic effect of different fucoidan extracts over melanoma cells, another commercially available fucoidan from Fucus vesiculosus was evaluated over five different uveal melanoma cells lines not showing antitumorigenic effects. 27 Based on the discrepancy of published results, in this study, we evaluated and validated the toxicity of soluble fucoidan not only over human melanoma cells (WM-115 cell line), but also over primary dermal fibroblasts and keratinocytes as models of the main cell types characterizing the tumor microenvironment. An alternative approach to face melanoma is herein proposed, aiming to decrease the cytotoxic effects over noncancer cells.…”

Fucoidan from Fucus vesiculosus inhibits new blood vessel formation and breast tumor growth in vivo

“…For example, in human hepatocarcinoma cells lines treated with different doses of fucoidan, angiogenesis was not affected and there was no decrease in VEGF expression (Zhu, Cao, Zhang, Man, & Wu, 2013). In another report, fucoidan did not present antitumor activity over uveal melanoma cells lines, demonstrating a pro-angiogenic potential instead (Dithmer et al, 2017).…”