Antitumor and antioxidant activities of levan and its derivative from the isolate Bacillus subtilis NRC1aza

Carbohydr Polym. 2012 Jun 20;89(2):314-22. doi: 10.1016/j.carbpol.2012.02.041. Epub 2012 Feb 25.

Abstract

The novel levansucrase produced from Bacillus subtilis NRC1aza yielded two types of levan L1 and L2 with different molecular weights 85.23 kDa and 31.95 kDa, respectively. The levan identification was detected by paper chromatography and high-pressure liquid chromatography. The antioxidant activity of levan and their derivatives (SL1 and SL2) exhibited a strong free radical scavenging activity with DPPH. The antitumor activity of SL1 was tested against different human cancer cell lines. The cell death was explored mechanistically through evaluation of Apoptosis/necrosis ratio, DNA fragmentation, histone deacetylase activity, mitochondrial transmembrane potential (Δψm), cytochrome C release, total caspases, caspase-3, and caspase-9, and cell cycle. SL1 showed high selective cytotoxicity against HepG2 cells. SL1 led to DNA damaging and fragmentation that was associated with induced apoptosis via mitochondrial pathway, which initiated by the impairment of Δψm and then increased mitochondria, released cytochrome c, that in turn activated caspase-9 and caspase-3 and induced apoptosis.

MeSH terms

  • Antineoplastic Agents / isolation & purification
  • Antineoplastic Agents / pharmacology*
  • Antioxidants / isolation & purification
  • Antioxidants / pharmacology*
  • Apoptosis / drug effects
  • Bacillus subtilis / metabolism*
  • Caspases / metabolism
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cytochromes c / metabolism
  • DNA Damage
  • Fructans / isolation & purification
  • Fructans / pharmacology*
  • Hexosyltransferases / metabolism
  • Histone Deacetylases / metabolism
  • Humans
  • Membrane Potential, Mitochondrial / drug effects
  • Oligosaccharides / isolation & purification
  • Oligosaccharides / pharmacology*
  • Polysaccharides, Bacterial / isolation & purification
  • Polysaccharides, Bacterial / pharmacology*

Substances

  • Antineoplastic Agents
  • Antioxidants
  • Fructans
  • Oligosaccharides
  • Polysaccharides, Bacterial
  • Cytochromes c
  • levan
  • Hexosyltransferases
  • levansucrase
  • Caspases
  • Histone Deacetylases