Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 386, Issue 11, pp 1009–1016

Phenethyl isothiocyanate induces apoptosis of cholangiocarcinoma cells through interruption of glutathione and mitochondrial pathway

Authors

  • Ornanong Tusskorn
    • Department of Pharmacology, Faculty of MedicineKhon Kaen University
  • Auemduan Prawan
    • Department of Pharmacology, Faculty of MedicineKhon Kaen University
    • Liver Fluke and Cholangiocarcinoma Research CenterKhon Kaen University
  • Laddawan Senggunprai
    • Department of Pharmacology, Faculty of MedicineKhon Kaen University
    • Liver Fluke and Cholangiocarcinoma Research CenterKhon Kaen University
  • Upa Kukongviriyapan
    • Department of Physiology, Faculty of MedicineKhon Kaen University
    • Department of Pharmacology, Faculty of MedicineKhon Kaen University
    • Liver Fluke and Cholangiocarcinoma Research CenterKhon Kaen University
Original Article

DOI: 10.1007/s00210-013-0906-8

Cite this article as:
Tusskorn, O., Prawan, A., Senggunprai, L. et al. Naunyn-Schmiedeberg's Arch Pharmacol (2013) 386: 1009. doi:10.1007/s00210-013-0906-8

Abstract

Phenethyl isothiocyanate (PEITC) is a natural isothiocyanate with anticancer activity against many drug-resistant cancer cells. A body of evidence suggests that PEITC enhances oxidative stress leading to cancer cell death. Cholangiocarcinoma (CCA) is an aggressive bile duct cancer with resistance to chemotherapeutic drugs. PEITC rapidly kills KKU-100 CCA cells with concurrent induction of cellular glutathione depletion, superoxide formation, and loss of mitochondrial transmembrane potential. The loss was associated with increased Bax and decreased Bcl-xl proteins followed by the release of cytochrome c and the activation of caspase-9 and -3. Although TEMPOL could prevent superoxide formation, it did not prevent the disruption of glutathione (GSH) redox, mitochondrial dysfunction, and cell death. On the other hand, N-acetylcysteine could prevent the events and cell death. It was concluded that disruption of GSH redox but not superoxide formation may be an initial step leading to mitochondrial injury. PEITC could be a promising chemopreventive agent for CCA.

Keywords

Phenethyl isothiocyanateCancer chemopreventionCholangiocarcinomaMitochondrial dysfunctionGlutathione

Abbreviations

BSO

Buthionine sulfoximine

TEMPOL

4-hydroxy-TEMPO

CCA

Cholangiocarcinoma

PEITC

Phenethyl isothiocyanate

GSH

Glutathione

GSSG

Glutathione disulfide

Ψm

Mitochondrial transmembrane potential

NAC

N-acetyl-L-cysteine

ROS

Reactive oxygen species

SRB

Sulforhodamine B

JC-1

5,5′,6,′-Tetrachloro-1,1′,3,3′-tetraethylbenzimidazolyl-carbocyanine iodide

MOMP

Mitochondrial outer membrane permeabilization

Copyright information

© Springer-Verlag Berlin Heidelberg 2013