Cytotoxicity of oleanolic and ursolic acid derivatives toward hepatocellular carcinoma and evaluation of NF-κB involvement

Bioorg Chem. 2019 Sep:90:103054. doi: 10.1016/j.bioorg.2019.103054. Epub 2019 Jun 7.

Abstract

Oleanolic and ursolic acids are two ubiquitous isomeric triterpene phytochemicals known for their anticancer activity. A set of derivatives of the two compounds with a modified oxidation state and lipophylicity at C-3 and C-28 positions, were prepared and tested as anticancer agents versus the lines HepG2, Hep3B and HA22T/VGH of hepatocarcinoma, a strongly aggressive tumor that is not responsive toward the standard therapies. New derivatives containing a three carbons side chain on the C-3 position were synthetized in both stereoisomeric forms by the Barbier-Grignard procedure and three of them were found to be active toward all of the three targets. The implication of the transcriptional nuclear factor NF-κB in the mechanism of action was assessed for the more active compounds in the set, as hepatocellular carcinoma (HCC) cyto-types are known to overexpress NF-κB.

Keywords: Antitumor activity; HA22T/VGH; Hep3B; HepG2; NF−κB; Oleanolic acid; Ursolic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis
  • Carcinoma, Hepatocellular / drug therapy
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology*
  • Cell Proliferation
  • Humans
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology*
  • Malus / chemistry
  • NF-kappa B / metabolism*
  • Olea / chemistry
  • Oleanolic Acid / pharmacology*
  • Plant Extracts / pharmacology*
  • Triterpenes / pharmacology*
  • Tumor Cells, Cultured
  • Ursolic Acid

Substances

  • Antineoplastic Agents, Phytogenic
  • NF-kappa B
  • Plant Extracts
  • Triterpenes
  • Oleanolic Acid