In vitro antitumor effect of a lignan isolated from Combretum fruticosum, trachelogenin, in HCT-116 human colon cancer cells

Toxicol In Vitro. 2018 Mar:47:129-136. doi: 10.1016/j.tiv.2017.11.014. Epub 2017 Nov 22.

Abstract

The use of natural products in therapeutics has been growing over the years. Lignans are compounds with large pharmaceutical use, which has aroused interest in the search for new drugs to treat diseases. The present study evaluated the cytotoxicity of (-)-trachelogenin, a dibenzylbutyrolactone type lignan isolated from Combretum fruticosum, against several tumor and non-tumor cell lines using the MTT assay and its possible mechanism of action. (-)-Trachelogenin showed IC50 values ranging of 0.8-32.4μM in SF-295 and HL-60 cell lines, respectively and IC50 values >64μM in non-tumor cell lines. (-)-trachelogenin persistently induced autophagic cell death, with cytoplasmic vacuolization and formation of autophagosomes mediated by increasing LC3 activation and altering the expression levels of Beclin-1.

Keywords: Anticancer; Autophagy; Combretum fruticosum; Lignans.

Publication types

  • Comparative Study

MeSH terms

  • 4-Butyrolactone / adverse effects
  • 4-Butyrolactone / analogs & derivatives*
  • 4-Butyrolactone / chemistry
  • 4-Butyrolactone / isolation & purification
  • 4-Butyrolactone / pharmacology
  • Antineoplastic Agents, Phytogenic / adverse effects
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / isolation & purification
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Autophagosomes / drug effects
  • Autophagosomes / pathology
  • Autophagy / drug effects*
  • Beclin-1 / agonists
  • Beclin-1 / metabolism
  • Brazil
  • Cell Line
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / pathology
  • Combretum / chemistry*
  • Combretum / growth & development
  • Drug Discovery*
  • Ethnopharmacology
  • HCT116 Cells
  • Humans
  • Inhibitory Concentration 50
  • Medicine, Traditional
  • Microtubule-Associated Proteins / agonists
  • Microtubule-Associated Proteins / metabolism
  • Molecular Structure
  • Neoplasm Proteins / agonists
  • Neoplasm Proteins / metabolism
  • Plant Stems / chemistry*
  • Plant Stems / growth & development
  • Vacuoles / drug effects
  • Vacuoles / pathology

Substances

  • Antineoplastic Agents, Phytogenic
  • BECN1 protein, human
  • Beclin-1
  • MAP1LC3A protein, human
  • Microtubule-Associated Proteins
  • Neoplasm Proteins
  • trachelogenin
  • 4-Butyrolactone