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

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.

• Authors: Bing Zhao, Xiaomeng Li
• Journal: Oncology reports (Oncol Rep) Vol. 31 Issue 6 Pg. 2769-75 (Jun 2014) ISSN: 1791-2431 [Electronic] Greece
• PMID: 24700345 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Furans
• Proto-Oncogene Proteins c-bcl-2
• Pyrones
• Reactive Oxygen Species
• altholactone
• Proto-Oncogene Proteins c-akt
• p38 Mitogen-Activated Protein Kinases
• Caspase 3
• Acetylcysteine

Topics

• Acetylcysteine (administration & dosage)
• Apoptosis (drug effects)
• Caspase 3 (biosynthesis)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Furans (administration & dosage)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Mitochondria (drug effects, pathology)
• Proto-Oncogene Proteins c-akt (antagonists & inhibitors, metabolism)
• Proto-Oncogene Proteins c-bcl-2 (biosynthesis)
• Pyrones (administration & dosage)
• Reactive Oxygen Species (metabolism)
• Urinary Bladder Neoplasms (genetics, metabolism, pathology)
• p38 Mitogen-Activated Protein Kinases (biosynthesis)