Chitooligosaccharides display anti-tumor effects against human cervical cancer cells via the apoptotic and autophagic pathways

Carbohydr Polym. 2019 Nov 15:224:115171. doi: 10.1016/j.carbpol.2019.115171. Epub 2019 Aug 9.

Abstract

Gynecological cancers are the most commonly diagnosed forms of cancer among the female population. Chitooligosaccharides (COS)-hydrolysis products from chitosan-display high bioavailability, high water solubility, and low molecular weight properties. Here, we investigated the influence of COS on 11 gynecological tumor cell types, and subsequently elucidated molecular mechanisms through which the observed inhibition occurred. Initially, we used a controllable enzyme-membrane coupling reactor system to obtain COS with a high degree of polymerization; the yield of high-degree-polymerized COS (DP 5-12) obtained with this reactor system accounted for ∼75% yields (w/w). Using these COS materials, cell line assays showed that COS elicited the most significant anti-tumor activity against C33A cells, with anti-tumor mechanisms related to oxidative stress, as well as activation of intrinsic mitochondrial apoptosis and autophagic signaling. Thus, we provide experimental evidence to demonstrate how the enzyme-membrane coupling reactor system can generate COS that exert bioactivity against gynecological cancers.

Keywords: Apoptosis; Autophagy; Chitooligosaccharides; Enzyme-membrane coupling reactor; ROS production.

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Autophagy / drug effects*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Chitin / analogs & derivatives*
  • Chitin / chemistry
  • Chitin / pharmacology
  • Chitosan / chemistry
  • Female
  • Humans
  • Membrane Potential, Mitochondrial / drug effects
  • Oligosaccharides
  • Oxidative Stress / drug effects
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects
  • Uterine Cervical Neoplasms / pathology*

Substances

  • Antineoplastic Agents
  • Oligosaccharides
  • Reactive Oxygen Species
  • oligochitosan
  • Chitin
  • Chitosan