Discovery of gamma-mangostin from Garcinia mangostana as a potent and selective natural SIRT2 inhibitor

Bioorg Chem. 2020 Jan:94:103403. doi: 10.1016/j.bioorg.2019.103403. Epub 2019 Nov 4.

Abstract

Studies have suggested that sirtuin inhibition may have beneficial effects on several age-related diseases such as neurodegenerative disorders and cancer. Garcinia mangostana is a well-known tropical plant found mostly in South East Asia with several positive health effects. Some of its phytochemicals such as α-mangostin was found to be able to modulate sirtuin activity in mice and was implicated with inflammation, diabetes and obesity. However, comprehensive studies on sirtuin activity by the prenylated xanthones extracted from Garcinia mangostana have yet to be reported. The present study led to the discovery and identification of γ-mangostin as a potent and selective SIRT2 inhibitor. It was demonstrated that γ-mangostin was able to increase the α-tubulin acetylation in MDA-MD-231 and MCF-7 breast cancer cells. It was also found to possess potent antiproliferative activity against both cell lines. In addition, it was able to induce neurite outgrowth in the N2a cells.

Keywords: Alzheimer’s disease; Antitumor; Breast cancer; Mangostin; Sirtuin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / isolation & purification
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Discovery*
  • Drug Screening Assays, Antitumor
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / isolation & purification
  • Enzyme Inhibitors / pharmacology*
  • Garcinia mangostana / chemistry*
  • Humans
  • Molecular Docking Simulation
  • Molecular Structure
  • Sirtuin 2 / antagonists & inhibitors*
  • Sirtuin 2 / metabolism
  • Structure-Activity Relationship
  • Tumor Cells, Cultured
  • Xanthones / chemistry
  • Xanthones / isolation & purification
  • Xanthones / pharmacology*

Substances

  • Antineoplastic Agents, Phytogenic
  • Enzyme Inhibitors
  • Xanthones
  • SIRT2 protein, human
  • Sirtuin 2
  • mangostin