Structure-activity relationship of Triterpenes and derived Glycosides against cancer cells and mechanism of apoptosis induction

Nat Prod Res. 2018 Mar;32(6):654-661. doi: 10.1080/14786419.2017.1335725. Epub 2017 Jun 29.

Abstract

Triterpenoids possess a wide range of biological effects. Here, the cytotoxic activities of 55 triterpenes and derived glycosides against BEL-7404 and SGC-7901 cells were assessed, and structure-activity relationships were analysed accordingly. Nine of them effectively inhibited the two cell lines. In particular, compounds 49 and 52 inhibited BEL-7404 cells as efficiently as 5'-fluorouracil (IC50 values 0.46 and 1.48, respectively). Moreover, we found that compounds 49 and 52 induced apoptosis in BEL-7404 cells. Indeed, DNA fragmentation assay showed a time-dependent degradation of DNA after treatment of cells with compounds 49 and 52. In addition, Bax gene expression levels were increased after treatment with these compounds, in a concentration-dependent manner. Taken together, our findings suggested that compounds 49 and 52 induce apoptosis in BEL-7404 cells by upregulating the Bax gene without affecting Bcl-2 gene expression.

Keywords: BEL-7404 cells; SGC-7901 cells; Triterpenoids; apoptosis; bax gene; structure-activity relationship.

MeSH terms

  • Antineoplastic Agents, Phytogenic / chemistry*
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • DNA Fragmentation / drug effects
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glycosides / chemistry
  • Glycosides / pharmacology*
  • Humans
  • Inhibitory Concentration 50
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Structure-Activity Relationship*
  • Triterpenes / chemistry
  • Triterpenes / pharmacology*
  • bcl-2-Associated X Protein / genetics

Substances

  • Antineoplastic Agents, Phytogenic
  • BAX protein, human
  • Glycosides
  • Proto-Oncogene Proteins c-bcl-2
  • Triterpenes
  • bcl-2-Associated X Protein