Daphnanes diterpenes from the latex of Hura crepitans L. And activity against human colorectal cancer cells Caco-2

Bioorg Chem. 2020 Oct:103:104132. doi: 10.1016/j.bioorg.2020.104132. Epub 2020 Jul 23.

Abstract

Hura crepitans (Euphorbiaceae) is a tree from South America that produces an irritant latex used as a fish poison. A bio-guided fractionation of an ethanolic extract of the latex led to the isolation and structural identification of three known daphnane-type diterpenes (1-3) including huratoxin (1), together with two new analogs (4, 5). Compound 1 was found to exhibit significant and selective cell growth inhibition against the colorectal cancer cell line Caco-2, with morphological modifications suggesting formations mimicking the intestinal crypt architecture. The underlying mechanism of 1 was further investigated, in comparison with 12-O-tetradecanoylphorbol-13-acetate (TPA), revealing two different mechanisms.

Keywords: Colorectal cancer; Cytotoxicity; Daphnane diterpenes; Epithelial morphogenesis; Hura crepitans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / isolation & purification
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Caco-2 Cells
  • Cell Proliferation / drug effects
  • Density Functional Theory
  • Diterpenes / chemistry
  • Diterpenes / isolation & purification
  • Diterpenes / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Euphorbiaceae / chemistry*
  • Humans
  • Latex / chemistry*
  • Molecular Structure
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents, Phytogenic
  • Diterpenes
  • Latex
  • mezerein