A3 Adenosine Receptor-Mediated p53-Dependent Apoptosis in Lu-65 Human Lung Cancer Cells

Cellular Physiology and Biochemistry

关键词: A3 adenosine receptor;    p53;    Noxa;    Lu-65 lung cancer cell;    Apoptosis;   

DOI  :  10.1159/000339058

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

Background/Aims A₃ adenosine receptor mediates apoptosis in cancer cells via diverse signaling pathways. The present study examined A₃ adenosine receptor-mediated apoptosis in Lu-65 cells, a human giant cell lung carcinoma cell line. Methods MTT assay, TUNEL staining, real-time RT-PCR, Western blotting, and assay of caspase-3, -8, and -9 activities were carried out in Lu-65 cells, and A₃ adenosine receptor or p53 was knocked-down by transfecting each siRNA into cells. Results Extracellular adenosine induces Lu-65 cell apoptosis in a concentration (0.01-10 mM)-dependent manner, and the effect was inhibited by the A₃ adenosine receptor inhibitor MRS1191 or by knocking-down A₃ adenosine receptor or p53. Like adenosine, the A₃ adenosine receptor agonist 2-Cl-IB-MECA also induced Lu-65 cell apoptosis. Adenosine upregulated expression of p53 and Noxa mRNAs and activated caspase-3 and -9, but not caspase-8. Those adenosine effects were still inhibited by knocking-down A₃ adenosine receptor or p53. Conclusion The results of the present study show that adenosine upregulates p53 expression via A₃ adenosine receptor, to promote p53-dependent Noxa gene transcription, causing activation of caspase-9 and the effector caspase-3 to induce Lu-65 cell apoptosis.

【 授权许可】

CC BY-NC-ND