Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 386, Issue 11, pp 1009–1016 | Cite as

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

  • Ornanong Tusskorn
  • Auemduan Prawan
  • Laddawan Senggunprai
  • Upa Kukongviriyapan
  • Veerapol Kukongviriyapan
Original Article

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 isothiocyanate Cancer chemoprevention Cholangiocarcinoma Mitochondrial dysfunction Glutathione 

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

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Ornanong Tusskorn
    • 1
  • Auemduan Prawan
    • 1
    • 2
  • Laddawan Senggunprai
    • 1
    • 2
  • Upa Kukongviriyapan
    • 3
  • Veerapol Kukongviriyapan
    • 1
    • 2
  1. 1.Department of Pharmacology, Faculty of MedicineKhon Kaen UniversityKhon KaenThailand
  2. 2.Liver Fluke and Cholangiocarcinoma Research CenterKhon Kaen UniversityKhon KaenThailand
  3. 3.Department of Physiology, Faculty of MedicineKhon Kaen UniversityKhon KaenThailand

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