The mitochondrial effects of embelin are independent of its MAP kinase regulation: Role of p53 in conferring selectivity towards cancer cells

Mitochondrion. 2019 May:46:158-163. doi: 10.1016/j.mito.2018.04.007. Epub 2018 Apr 30.

Abstract

Amongst various therapeutic properties of the natural product embelin, its anti-cancer effects are being extensively studied. We observed that, embelin induced apoptosis in A549 cells lacking functional mitochondria (ρ0 cells) indicating that its mitochondrial effects are not primarily responsible for its anti-cancer activity. However, p38 mediated activation of p53 was found to play a pivotal role in governing the apoptotic activity of embelin due to the following observations: a time-dependent activation of p53 and apoptosis by embelin; selective inhibition of p38 inhibited embelin-induced p53 levels. Overall, therapeutic strategies involving embelin and activators of p38 MAP kinase may improve the selective targeting of cancer cells.

Keywords: Apoptosis; Embelin; Mitochondrial respiration; Oxidative stress; p38 MAP kinase; p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Antineoplastic Agents / metabolism*
  • Apoptosis
  • Benzoquinones / metabolism*
  • Epithelial Cells / drug effects*
  • Humans
  • Neoplasms / pathology*
  • Tumor Suppressor Protein p53 / metabolism*
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Antineoplastic Agents
  • Benzoquinones
  • Tumor Suppressor Protein p53
  • p38 Mitogen-Activated Protein Kinases
  • embelin