Enhancement of arsenic trioxide-induced apoptosis in HeLa cells by diethyldithiocarbamate or buthionine sulfoximine

  • Authors:
    • Yong Hwan Han
    • Sung Zoo Kim
    • Suhn Hee Kim
    • Woo Hyun Park
  • View Affiliations

  • Published online on: July 1, 2008     https://doi.org/10.3892/ijo.33.1.205
  • Pages: 205-213
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Arsenic trioxide (ATO) affects many biological functions such as cell proliferation, apoptosis, differentiation and angiogenesis in various cells. We investigated the in vitro effects of ATO as a reactive oxygen species (ROS) generator or a glutathione (GSH) depletor on apoptosis in HeLa cells. ATO decreased the viability of HeLa cells in a dose-dependent manner with an IC50 of approximately 5-6 µM. ATO triggered apoptosis, which is accompanied by the loss of mitochondrial transmembrane potential (ΔΨm). Intracellular general ROS levels in HeLa cells were increased or decreased depending on the concentration of ATO. Particularly, the levels of O2·- were increased by ATO. In addition, we detected a decreased GSH content in ATO-treated cells. The GSH-depleted cells mainly showed propidium iodine-positive staining, indicating that the majority of the cells were dead. Diethyldithiocarbamate (DDC; an inhibitor of Cu,Zn-SOD) induced apoptosis and the loss of mitochondrial transmembrane potential (ΔΔΨm) in HeLa control cells. DDC intensified apoptosis, the loss of mitochondrial transmembrane potential, increased levels of O22·- and GSH depletion in ATO-treated cells. L-buthionine sulfoximine (BSO; an inhibitor of GSH synthesis) did not induce apoptosis in HeLa control cells, but increased levels of apoptosis, O22·- and GSH depletion in ATO-treated cells. In conclusion, the changes in intracellular GSH levels rather than ROS levels are tightly related to the enhancement of ATO-induced apoptosis in HeLa cells by DDC or BSO.

Related Articles

Journal Cover

July 2008
Volume 33 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Han YH, Kim SZ, Kim SH and Park WH: Enhancement of arsenic trioxide-induced apoptosis in HeLa cells by diethyldithiocarbamate or buthionine sulfoximine. Int J Oncol 33: 205-213, 2008
APA
Han, Y.H., Kim, S.Z., Kim, S.H., & Park, W.H. (2008). Enhancement of arsenic trioxide-induced apoptosis in HeLa cells by diethyldithiocarbamate or buthionine sulfoximine. International Journal of Oncology, 33, 205-213. https://doi.org/10.3892/ijo.33.1.205
MLA
Han, Y. H., Kim, S. Z., Kim, S. H., Park, W. H."Enhancement of arsenic trioxide-induced apoptosis in HeLa cells by diethyldithiocarbamate or buthionine sulfoximine". International Journal of Oncology 33.1 (2008): 205-213.
Chicago
Han, Y. H., Kim, S. Z., Kim, S. H., Park, W. H."Enhancement of arsenic trioxide-induced apoptosis in HeLa cells by diethyldithiocarbamate or buthionine sulfoximine". International Journal of Oncology 33, no. 1 (2008): 205-213. https://doi.org/10.3892/ijo.33.1.205