Low-molecular-weight fucoidan inhibits the proliferation of melanoma via Bcl-2 phosphorylation and PTEN/AKT pathway

Oncol Res. 2023 Dec 28;32(2):273-282. doi: 10.32604/or.2023.044362. eCollection 2023.

Abstract

Fucoidan, a sulfate polysaccharide obtained from brown seaweed, has various bioactive properties, including anti-inflammatory, anti-cancer, anti-viral, anti-oxidant, anti-coagulant, anti-thrombotic, anti-angiogenic, and anti-Helicobacter pylori properties. However, the effects of low-molecular-weight fucoidan (LMW-F) on melanoma cell lines and three dimensional (3D) cell culture models are not well understood. This study aimed to investigate the effects of LMW-F on A375 human melanoma cells and cryopreserved biospecimens derived from patients with advanced melanoma. Ultrasonic wave was used to fragment fucoidan derived from Fucus vesiculosus into smaller LMW-F. MTT and live/dead assays showed that LMW-F inhibited cell proliferation in both A375 cells and patient-derived melanoma explants in a 3D-printed collagen scaffold. The PTEN/AKT pathway was found to be involved in the anti-melanoma effects of fucoidan. Western blot analysis revealed that LMW-F reduced the phosphorylation of Bcl-2 at Thr 56, which was associated with the prevention of anti-apoptotic activity of cancer cells. Our findings suggested that LMW-F could enhance anti-melanoma chemotherapy and improve the outcomes of patients with melanoma resistance.

Keywords: Anti-melanoma effect; Low-molecular-weight fucoidan; Melanoma; PTEN-AKT-Bcl-2 network; Patient-derived melanoma explants in a 3D-printed collagen scaffold.

MeSH terms

  • Antineoplastic Agents* / pharmacology
  • Antioxidants
  • Cell Proliferation
  • Humans
  • Melanoma* / drug therapy
  • PTEN Phosphohydrolase
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt

Substances

  • fucoidan
  • Proto-Oncogene Proteins c-akt
  • Antineoplastic Agents
  • Antioxidants
  • PTEN protein, human
  • PTEN Phosphohydrolase