A3 adenosine receptor antagonist, truncated Thio-Cl-IB-MECA, induces apoptosis in T24 human bladder cancer cells.

Abstract

BACKGROUND:

Human A(3) adenosine receptor (A(3)AR) plays an essential role in several physiopathological processes. Thus far, A(3)AR-selective ligands have been evaluated as anti-inflammation and anticancer therapeutic agents. Among these ligands, truncated thio-Cl-IB-MECA is a newly reported antagonist, and its function has not been studied.

MATERIALS AND METHODS:

Cell viability was measured by MTS assay. Cell cycle progression was analysed by propidium iodide (PI) flow cytometric assay. The apoptotic effects were investigated by Hoechst staining and annexin V-FITC/PI staining. The signal-transduction mechanism was explored by Western blot.

RESULTS:

Truncated thio-Cl-IB-MECA induced the growth arrest of T24 cells at sub-G(1) phase and provoked apoptosis but not necrosis. Apoptotic death was mediated by the activation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK).

CONCLUSION:

Since truncated thio-Cl-IB-MECA induces anti-proliferation and apoptotic effects via ERK and JNK activation, it may function as an anticancer agent in human bladder cancer cells.

• Authors: Heejong Kim, Jeong Woo Kang, Sojung Lee, Won Jun Choi, Lak Shin Jeong, Young Yang, Jin Tae Hong, Do Young Yoon
• Journal: Anticancer research (Anticancer Res) Vol. 30 Issue 7 Pg. 2823-30 (Jul 2010) ISSN: 1791-7530 [Electronic] Greece
• PMID: 20683018 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adenosine A3 Receptor Antagonists
• BAX protein, human
• Proto-Oncogene Proteins c-bcl-2
• bcl-2-Associated X Protein
• thio-Cl-IB-MECA
• Cytochromes c
• Extracellular Signal-Regulated MAP Kinases
• MAP Kinase Kinase 4
• Caspases
• Adenosine

Topics

• Adenosine (analogs & derivatives, pharmacology)
• Adenosine A3 Receptor Antagonists
• Apoptosis (drug effects)
• Caspases (metabolism)
• Cell Cycle (drug effects)
• Cell Growth Processes (drug effects)
• Cell Line, Tumor
• Cytochromes c (metabolism)
• Enzyme Activation (drug effects)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• G1 Phase (drug effects)
• Humans
• MAP Kinase Kinase 4 (metabolism)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Urinary Bladder Neoplasms (drug therapy, metabolism, pathology)
• bcl-2-Associated X Protein (metabolism)