Altholactone induces reactive oxygen species-mediated apoptosis in bladder cancer T24 cells through mitochondrial dysfunction, MAPK-p38 activation and Akt suppression

  • Authors:
    • Bing Zhao
    • Xiaomeng Li
  • View Affiliations

  • Published online on: April 3, 2014     https://doi.org/10.3892/or.2014.3126
  • Pages: 2769-2775
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Human bladder cancer is an aggressive tumor which frequently resists chemotherapy. Therefore, the search for new therapeutic agents is of great importance. Altholactone, isolated from Goniothalamus sp., has been reported to inhibit the growth of various types of cancer cells. However, no prior research has been conducted to demonstrate the antiproliferative potential of altholactone on bladder cancer. In the present study, we characterized the effect of altholactone on cell growth and apoptosis in bladder cancer T24 cells. Treatment with altholactone resulted in a significant reduction in cell viability, induction of apoptosis and generation of reactive oxygen species (ROS) in T24 cells. Furthermore, our results revealed that altholactone-induced apoptosis was associated with decreased expression of Akt phosphorylation and activation of MAPK‑p38. Altholactone treatment was also found to result in a significant loss of mitochondrial membrane potential, Bcl-2 downregulation and caspase-3 activation. Pretreatment of T24 cells with the antioxidant N-acetylcysteine (NAC) significantly inhibited activation of caspase-3 and MAPK-p38 and prevented inactivation of Akt and Bcl-2. Taken together, our data demonstrate that altholactone induces ROS-dependent apoptosis in T24 cells via a novel mechanism involving inhibition of Akt and provide the rationale for further in vivo and preclinical investigation of altholactone against bladder cancer.

Related Articles

Journal Cover

June-2014
Volume 31 Issue 6

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
Zhao B and Zhao B: Altholactone induces reactive oxygen species-mediated apoptosis in bladder cancer T24 cells through mitochondrial dysfunction, MAPK-p38 activation and Akt suppression. Oncol Rep 31: 2769-2775, 2014
APA
Zhao, B., & Zhao, B. (2014). Altholactone induces reactive oxygen species-mediated apoptosis in bladder cancer T24 cells through mitochondrial dysfunction, MAPK-p38 activation and Akt suppression. Oncology Reports, 31, 2769-2775. https://doi.org/10.3892/or.2014.3126
MLA
Zhao, B., Li, X."Altholactone induces reactive oxygen species-mediated apoptosis in bladder cancer T24 cells through mitochondrial dysfunction, MAPK-p38 activation and Akt suppression". Oncology Reports 31.6 (2014): 2769-2775.
Chicago
Zhao, B., Li, X."Altholactone induces reactive oxygen species-mediated apoptosis in bladder cancer T24 cells through mitochondrial dysfunction, MAPK-p38 activation and Akt suppression". Oncology Reports 31, no. 6 (2014): 2769-2775. https://doi.org/10.3892/or.2014.3126