Role of p38 MAPK and JNK in enhanced cervical cancer cell killing by the combination of arsenic trioxide and ionizing radiation

  • Authors:
    • Young-Hee Kang
    • Su-Jae Lee
  • View Affiliations

  • Published online on: September 1, 2008     https://doi.org/10.3892/or_00000053
  • Pages: 637-643
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Enhancement of radiation response is possible to be achieved by combination treatment with therapeutic drugs. Previously we have shown that As2O3 in combination with ionizing radiation enhanced radiation response in cervical cancer cells. In this study, we further investigated molecular mechanism of synergistic enhancement of radiation response in combination with As2O3. The combination treatment of HeLa cells induced translocation of Bax to the mitochondria and a marked phosphorylation of Bcl-2. p38 MAPK and JNK were also found to be activated in response to the combination treatment. Pretreatment of PD169316, a p38 MAPK specific inhibitor, completely attenuated the combination treatment-induced mitochondrial relocalization of Bax, and altered Bcl-2 phosphorylation. Moreover, pretreatment of SP600125, JNK specific inhibitor, clearly attenuated Bcl-2 phosphorylation, but did not affect Bax translocation to the mitochondria. In addition, N-acetyl-L-cysteine (NAC), a thiol-containing anti-oxidant, completely blocked p38 MAPK and JNK activations, Bax relocalization and Bcl-2 phosphorylation. These results indicate that activation of p38 MAPK is specifically required for translocation of Bax to the mitochondria, and both JNK and p38 MAPK are involved in phosphorylation of Bcl-2 in response to combination treatment with γ-radiation and As2O3, and that ROS is a critical regulator of p38 MAPK and JNK activations. The molecular mechanism elucidated in this study may provide insight into the design of future combination cancer therapies to cells intrinsically less sensitive to radiation treatment.

Related Articles

Journal Cover

September 2008
Volume 20 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Kang Y and Kang Y: Role of p38 MAPK and JNK in enhanced cervical cancer cell killing by the combination of arsenic trioxide and ionizing radiation. Oncol Rep 20: 637-643, 2008
APA
Kang, Y., & Kang, Y. (2008). Role of p38 MAPK and JNK in enhanced cervical cancer cell killing by the combination of arsenic trioxide and ionizing radiation. Oncology Reports, 20, 637-643. https://doi.org/10.3892/or_00000053
MLA
Kang, Y., Lee, S."Role of p38 MAPK and JNK in enhanced cervical cancer cell killing by the combination of arsenic trioxide and ionizing radiation". Oncology Reports 20.3 (2008): 637-643.
Chicago
Kang, Y., Lee, S."Role of p38 MAPK and JNK in enhanced cervical cancer cell killing by the combination of arsenic trioxide and ionizing radiation". Oncology Reports 20, no. 3 (2008): 637-643. https://doi.org/10.3892/or_00000053