Different cell death responses induced by eupomatenoid-5 in MCF-7 and 786-0 tumor cell lines

Toxicol In Vitro. 2015 Aug;29(5):1026-33. doi: 10.1016/j.tiv.2015.04.002. Epub 2015 Apr 13.

Abstract

Natural products remain an important source of new drugs, including anticancer drugs. Recently, our group reported the anticancer activity of eupomatenoid-5 (eup-5), a neolignan isolated from Piper regnellii (Miq.) C. DC. var. regnellii leaves. In vitro studies demonstrated that MCF-7 (breast) and 786-0 (kidney) were among the cancer cell lines most sensitive to eup-5 treatment. The current results demonstrate that mitochondrial membrane depolarization and generation of reactive oxygen species are implicated in eup-5-mediated cytotoxic effects on these cancer cells lines. In MCF-7 cells, eup-5 led to phosphatidylserine externalization and caspase activation, whereas the same did not occur in 786-0 cells. Scanning electron microscopy revealed a reduction of microvilli density, as well as cell morphology alterations. Moreover, treated MCF-7 cells exhibited well-characterized apoptosis alterations, while treated 786-0 cells exhibited characteristics of programmed necroptosis process. These findings support the possibility that different mechanisms may be targeted by eup-5 in cell death response.

Keywords: 786-0; Apoptosis; Eupomatenoid-5; MCF-7; Piper regnellii; Programmed necrosis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Benzofurans / pharmacology*
  • Caspases / metabolism
  • Cell Death / drug effects
  • Cell Line, Tumor
  • Humans
  • Hydrogen Peroxide / metabolism
  • Membrane Potential, Mitochondrial / drug effects
  • Phenols / pharmacology*
  • Phosphatidylserines / metabolism
  • Piper
  • Plant Leaves
  • Superoxides / metabolism

Substances

  • Antineoplastic Agents, Phytogenic
  • Benzofurans
  • Phenols
  • Phosphatidylserines
  • Superoxides
  • eupomatenoid 5
  • Hydrogen Peroxide
  • Caspases