Asaroidoxazines from the Roots of Asarum asaroides Induce Apoptosis in Human Neuroblastoma Cells

J Nat Prod. 2020 Oct 23;83(10):3050-3057. doi: 10.1021/acs.jnatprod.0c00574. Epub 2020 Sep 21.

Abstract

Plants in the family Aristolochiaceae contain phenanthrene skeleton-containing chemical constituents that exhibit nephrotoxic, carcinogenic, mutagenic, anti-inflammatory, and cytotoxic effects. Two new phenanthrene-containing 1,2-oxazin-6-ones, designated as asaroidoxazine A (1) and asaroidoxazine B (2), and a known aristolactam, 5-methoxyaristololactam I (3), were isolated from the roots of Asarum asaroides. The structures of compounds 1 and 2 were determined using spectroscopic methods and X-ray crystallography. Treatment of SH-SY5Y human neuroblastoma cells with 1 μM of asaroidoxazine A (1) induced nuclear condensation as well as caspase-3/7 activation, indicating that this compound is a strong apoptosis inducer in neuronal cells. This is the first report of apoptosis induction by phenanthrene-containing oxazines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • Asarum / chemistry*
  • Brain Neoplasms / drug therapy*
  • Caspases / drug effects
  • Cell Line, Tumor
  • Cell Nucleus / drug effects
  • Cell Nucleus / ultrastructure
  • Enzyme Activation / drug effects
  • Humans
  • Molecular Structure
  • Neuroblastoma / drug therapy*
  • Phenanthrenes / chemistry
  • Phenanthrenes / pharmacology
  • Plant Roots / chemistry*
  • X-Ray Diffraction

Substances

  • Antineoplastic Agents, Phytogenic
  • Phenanthrenes
  • Caspases