Glucuronorhamnoxylan from Capsosiphon fulvescens inhibits the growth of HT-29 human colon cancer cells in vitro and in vivo via induction of apoptotic cell death

Int J Biol Macromol. 2019 Mar 1:124:1060-1068. doi: 10.1016/j.ijbiomac.2018.12.001. Epub 2018 Dec 3.

Abstract

Colorectal cancer is the third most diagnosed cancer and a leading cause of cancer death. Dissatisfaction with currently available anti-colorectal cancer drugs caused by unwanted side effects and low efficacy necessitates new therapeutic agents. In the present study, a sulfated glucuronorhamnoxylan polysaccharide (named SPS-CF) purified from a green alga Capsosiphon fulvescens was evaluated for its anti-cancer activity in vitro and in vivo against colorectal cancer. The SPS-CF treatment resulted in a dose-dependent inhibition of the HT-29 human colon cancer cell growth up to 40% at 500 μg/mL. This inhibitory activity was shown to be mediated by upregulation of the cleavage of caspase-8, -9, -3 and poly (ADP-ribose) polymerase (PARP), induction of DNA fragmentation, and disruption of mitochondrial membrane potential (MMP), demonstrating that SPS-CF causes apoptotic death of HT-29 cancer cells though activation of caspase-dependant pathway. Administration of SPS-CF to BALB/c-nude mice bearing HT-29 cell-xenograft tumor also reduced the tumor growth. The results of this study demonstrated that the SPS-CF effectively inhibits the colorectal tumor growth both in vitro and in vivo by induction of apoptotic death of tumor cells, suggesting that it can be a potent ingredient for health-beneficial foods or anti-cancer agents to prevent or ameliorate human colon cancer.

Keywords: Apoptosis; Colon cancer; Glucuronorhamnoxylan.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins / metabolism
  • Chlorophyta / chemistry*
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • HT29 Cells
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Proteins / metabolism
  • Polysaccharides / chemistry
  • Polysaccharides / pharmacology*
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents, Phytogenic
  • Apoptosis Regulatory Proteins
  • Neoplasm Proteins
  • Polysaccharides