Degradation of Sargassum crassifolium Fucoidan by Ascorbic Acid and Hydrogen Peroxide, and Compositional, Structural, and In Vitro Anti-Lung Cancer Analyses of the Degradation Products

Mar Drugs. 2020 Jun 26;18(6):334. doi: 10.3390/md18060334.

Abstract

Fucoidans possess multiple biological functions including anti-cancer activity. Moreover, low-molecular-weight fucoidans are reported to possess more bioactivities than native fucoidans. In the present study, a native fucoidan (SC) was extracted from Sargassum crassifolium pretreated by single-screw extrusion, and three degraded fucoidans, namely, SCA (degradation of SC by ascorbic acid), SCH (degradation of SC by hydrogen peroxide), and SCAH (degradation of SC by ascorbic acid + hydrogen peroxide), were produced. The extrusion pretreatment can increase the extraction yield of fucoidan by approximately 4.2-fold as compared to the non-extruded sample. Among SC, SCA, SCH, and SCAH, the chemical compositions varied but structural features were similar. SC, SCA, SCH, and SCAH showed apoptotic effects on human lung carcinoma A-549 cells, as illustrated by loss of mitochondrial membrane potential (MMP), decreased B-cell leukemia-2 (Bcl-2) expression, increased cytochrome c release, increased active caspase-9 and -3, and increased late apoptosis of A-549 cells. In general, SCA was found to exhibit high cytotoxicity to A-549 cells and a strong ability to suppress Bcl-2 expression. SCA also showed high efficacy to induce cytochrome c release, activate caspase-9 and -3, and promote late apoptosis of A-549 cells. Therefore, our data suggest that SCA could have an adjuvant therapeutic potential in the treatment of lung cancer. Additionally, we explored that the Akt/mammalian target of rapamycin (mTOR) signaling pathway is involved in SC-, SCA-, SCH-, and SCAH-induced apoptosis of A-549 cells.

Keywords: Sargassum crassifolium; anti-lung cancer; apoptosis; ascorbic acid; brown algae; fucoidan; human lung carcinoma A-549 cells; hydrogen peroxide.

MeSH terms

  • Apoptosis / drug effects
  • Ascorbic Acid / pharmacology*
  • Caspases / metabolism
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cytochromes c / metabolism
  • Humans
  • Hydrogen Peroxide / pharmacology*
  • Lung Neoplasms
  • Membrane Potential, Mitochondrial / drug effects
  • Polysaccharides / chemistry*
  • Polysaccharides / pharmacology*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Sargassum / chemistry*
  • Signal Transduction
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • BCL2 protein, human
  • Polysaccharides
  • Proto-Oncogene Proteins c-bcl-2
  • Cytochromes c
  • fucoidan
  • Hydrogen Peroxide
  • MTOR protein, human
  • AKT1 protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • Caspases
  • Ascorbic Acid