Berberine induces mitochondrial apoptosis of EBV-transformed B cells through p53-mediated regulation of XAF1 and GADD45α

  • Authors:
    • Ga Bin Park
    • Sang Hyun Park
    • Daejin Kim
    • Yeong Seok Kim
    • Sung Ho Yoon
    • Dae Young Hur
  • View Affiliations

  • Published online on: April 26, 2016     https://doi.org/10.3892/ijo.2016.3502
  • Pages: 411-421
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Berberine exhibits antiproliferative or cytotoxic effects against various cancers. ROS and wild-type p53 play a critical role in berberine-induced cytotoxic effects. In this study, we investigated the correlation between XAF1 and functional p53 in EBV-transformed B cells or cancerous B cells after treatment with berberine. Berberine decreased cell viability and induced apoptosis through a mitochondria-dependent pathway in EBV-transformed B cells and cancerous B cells, but not in normal peripheral blood mononuclear cells. Activated p53 and its downstream targets XAF1 and GADD45α interacted with PUMA, Bax, and Bim in mitochondria after treatment with berberine. Blocking phosphorylation of p38/JNK MAPK and treatment with PFT-α, a selective p53 inhibitor, effectively prevented apoptosis and the upregulation of phosphorylated p53, XAF1, and GADD45α. NAC, a ROS scavenger, also suppressed berberine-induced mitochondria disruption and the whole apoptotic process via restoration of p53-related proteins and proapoptotic Bcl-2 family proteins. Taken together, our results suggest that ROS generation might be a predisposing event in berberine-induced mitochondrial apoptosis in EBV-transformed B cells through the upregulation of XAF1 and GADD45α expression by MAPK and functional p53.
View Figures
View References

Related Articles

Journal Cover

July-2016
Volume 49 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
Park GB, Park SH, Kim D, Kim YS, Yoon SH and Hur DY: Berberine induces mitochondrial apoptosis of EBV-transformed B cells through p53-mediated regulation of XAF1 and GADD45α. Int J Oncol 49: 411-421, 2016
APA
Park, G.B., Park, S.H., Kim, D., Kim, Y.S., Yoon, S.H., & Hur, D.Y. (2016). Berberine induces mitochondrial apoptosis of EBV-transformed B cells through p53-mediated regulation of XAF1 and GADD45α. International Journal of Oncology, 49, 411-421. https://doi.org/10.3892/ijo.2016.3502
MLA
Park, G. B., Park, S. H., Kim, D., Kim, Y. S., Yoon, S. H., Hur, D. Y."Berberine induces mitochondrial apoptosis of EBV-transformed B cells through p53-mediated regulation of XAF1 and GADD45α". International Journal of Oncology 49.1 (2016): 411-421.
Chicago
Park, G. B., Park, S. H., Kim, D., Kim, Y. S., Yoon, S. H., Hur, D. Y."Berberine induces mitochondrial apoptosis of EBV-transformed B cells through p53-mediated regulation of XAF1 and GADD45α". International Journal of Oncology 49, no. 1 (2016): 411-421. https://doi.org/10.3892/ijo.2016.3502