Critical roles of intracellular thiols and calcium in parthenolide-induced apoptosis in human colorectal cancer cells

Siyuan Zhang, Choon Nam Ong, Han Ming Shen

Research output: Contribution to journalArticlepeer-review

415 Scopus citations

Abstract

Parthenolide is one of the main components responsible for the anti-inflammatory property of Feverfew. Recently, parthenolide has shown to induce apoptosis in cancer cells. Here we further studied the mechanism of parthenolide-induced apoptosis by focusing on the role of intracellular thiols and calcium in a human colorectal cancer cell, COLO 205. Parthenolide rapidly depleted intracellular thiols, including both free glutathione (GSH) and protein thiols. Concomitantly, there were dose- and time-dependent increases in intracellular reactive oxygen species (ROS) and calcium levels. Increased expression of GRP78 protein, a marker for endoplasmic reticulum stress was also detected. All these changes preceded parthenolide-induced apoptotic cell death. More importantly, pretreatment with N-acetylcysteine, a precursor of GSH synthesis, protected the cells from parthenolide-induced thiol depletion, ROS production, cytosolic calcium increase and completely blocked parthenolide-induced apoptosis. On the contrary, pretreatment of buthionine sulfoximine, an inhibitor of GSH synthesis sensitized the cell to apoptosis. These data clearly demonstrate that the intracellular thiols and calcium equilibrium play a critical role in parthenolide-induced apoptotic cell death.

Original languageEnglish (US)
Pages (from-to)143-153
Number of pages11
JournalCancer Letters
Volume208
Issue number2
DOIs
StatePublished - May 28 2004
Externally publishedYes

Keywords

  • AO, acridine orange
  • Apoptosis
  • BSO, buthionine sulfoximine
  • Calcium
  • EB, ethidium bromide
  • Glutathione
  • GSH, reduced glutathione
  • GSSG, oxidized glutathione
  • NAC, N-acetylcysteine
  • Parthenolide
  • PN, parthenolide
  • Reactive oxygen species
  • Thiol

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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