A(3) Adenosine Receptor-Mediated p53-Dependent Apoptosis in Lu-65 Human Lung Cancer Cells

作者：Otsuki Tai ichiro; Kanno Takeshi; Fujita Yumiko; Tabata Chiharu; Fukuoka Kazuya; Nakano Takashi; Gotoh Akinobu; Nishizaki Tomoyuki^*

来源：Cellular Physiology and Biochemistry, 2012, 30(1): 210-220.

DOI：10.1159/000339058

• A(3) adenosine receptor
• p53
• Noxa
• Lu-65 lung cancer cell
• Apoptosis

Background/Aims: A(3) adenosine receptor mediates apoptosis in cancer cells via diverse signaling pathways. The present study examined A(3) 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 A(3) 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 A(3) adenosine receptor inhibitor MRS1191 or by knocking-down A(3) adenosine receptor or p53. Like adenosine, the A(3) 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 A(3) adenosine receptor or p53. Conclusion: The results of the present study show that adenosine upregulates p53 expression via A(3) 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.

• 出版日期2012