Journal of Bioenergetics and Biomembranes

, Volume 40, Issue 6, pp 607–618

Role of reactive oxygen species-mediated mitochondrial dysregulation in 3-bromopyruvate induced cell death in hepatoma cells

ROS-mediated cell death by 3-BrPA
  • Ji Su Kim
  • Keun Jae Ahn
  • Jeong-Ah Kim
  • Hye Mi Kim
  • Jong Doo Lee
  • Jae Myun Lee
  • Se Jong Kim
  • Jeon Han Park
Article

DOI: 10.1007/s10863-008-9188-0

Cite this article as:
Kim, J.S., Ahn, K.J., Kim, JA. et al. J Bioenerg Biomembr (2008) 40: 607. doi:10.1007/s10863-008-9188-0

Abstract

Hexokinase type II (HK II) is the key enzyme for maintaining increased glycolysis in cancer cells where it is overexpressed. 3-bromopyruvate (3-BrPA), an inhibitor of HK II, induces cell death in cancer cells. To elucidate the molecular mechanism of 3-BrPA-induced cell death, we used the hepatoma cell lines SNU449 (low expression of HKII) and Hep3B (high expression of HKII). 3-BrPA induced ATP depletion-dependent necrosis and apoptosis in both cell lines. 3-BrPA increased intracellular reactive oxygen species (ROS) leading to mitochondrial dysregulation. NAC (N-acetyl-l-cysteine), an antioxidant, blocked 3-BrPA-induced ROS production, loss of mitochondrial membrane potential and cell death. 3-BrPA-mediated oxidative stress not only activated poly-ADP-ribose (PAR) but also translocated AIF from the mitochondria to the nucleus. Taken together, 3-BrPA induced ATP depletion-dependent necrosis and apoptosis and mitochondrial dysregulation due to ROS production are involved in 3-BrPA-induced cell death in hepatoma cells.

Keywords

3-bromopyruvate ATP depletion-dependent necrosis Apoptosis ROS Mitochondrial dysregulation 

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Ji Su Kim
    • 1
    • 5
  • Keun Jae Ahn
    • 2
  • Jeong-Ah Kim
    • 3
    • 6
  • Hye Mi Kim
    • 4
  • Jong Doo Lee
    • 2
  • Jae Myun Lee
    • 1
  • Se Jong Kim
    • 1
  • Jeon Han Park
    • 1
  1. 1.Department of Microbiology and Brain Korea 21 Project for Medical Sciences, Institute for Immunology and Immunological DiseasesYonsei University College of MedicineSeoulSouth Korea
  2. 2.Division of Nuclear Medicine, Department of Diagnostic RadiologyYonsei University College of MedicineSeoulSouth Korea
  3. 3.Department of Radiology, Cheil General Hospital and Women’s Healthcare CenterKwandong University College of MedicineSeoulSouth Korea
  4. 4.Department of Diagnostic RadiologyYonsei University College of MedicineSeoulSouth Korea
  5. 5.Yonsei Cancer Research InstituteYonsei University College of MedicineSeoulSouth Korea
  6. 6.Department of Radiology, Yongdong Severance HospitalYonsei University College of MedicineSeoulSouth Korea