title: AMP converted from intracellularly transported adenosine upregulates p53 expression to induce malignant pleural mesothelioma cell apoptosis.
abstract: OBJECTIVE
  The present study investigated adenosine-induced apoptosis in human malignant pleural mesothelioma cells.
  
  
  METHODS
  MTT assay, TUNEL staining, flow cytometry using propidium iodide and annexin V-FITC, real-time RT-PCR, Western blotting, and assay of caspase-3, -8, and -9 activities were carried out using malignant pleural mesothelioma cell lines such as NCI-H28, NCI-H2052, NCI-H2452, and MSTO-211H cells, and p53 or A(3) adenosine receptor was knocked-down by transfecting each siRNA into cells.
  
  
  RESULTS
  Adenosine induced apoptosis in all the malignant pleural mesothelioma cells used here, independently of caspase activation. The adenosine effect was prevented by the adenosine transporter inhibitor dipyridamole, the adenosine kinase inhibitor ABT-702, or the A(3) adenosine receptor inhibitor MRS1191. Adenosine upregulated expression of the p53 mRNA and protein, that is abolished by ABT-702, but not by knocking-down A(3) adenosine receptor. Adenosine-induced apoptosis in NCI-H28 cells was significantly inhibited by knocking-down p53 and in part by knocking-down A(3) adenosine receptor.
  
  
  CONCLUSIONS
  The results of the present study show that AMP converted from intracellularly transported adenosine upregulates p53 expression to induce caspase-independent apoptosis in malignant pleural mesothelioma cells and that A(3) adenosine receptor also participates partially in the apoptosis by the different mechanism.
authors: Division of Bioinformation, Department of Physiology, Hyogo College of Medicine, Mukogawa-cho, Nishinomiya, Japan.
authors: Yoshitaka
authors: Y
authors: Nogi
authors: Takeshi
authors: T
authors: Kanno
authors: Takashi
authors: T
authors: Nakano
authors: Yumiko
authors: Y
authors: Fujita
authors: Chiharu
authors: C
authors: Tabata
authors: Kazuya
authors: K
authors: Fukuoka
authors: Akinobu
authors: A
authors: Gotoh
authors: Tomoyuki
authors: T
authors: Nishizaki
mesh_terms: D000241:Adenosine / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D058916:Adenosine A1 Receptor Antagonists / Q000494:pharmacology; D058917:Adenosine A2 Receptor Antagonists / Q000494:pharmacology; D058918:Adenosine A3 Receptor Antagonists / Q000494:pharmacology; D000249:Adenosine Monophosphate / Q000378:metabolism* / Q000502:physiology; D017209:Apoptosis; D051033:Apoptosis Inducing Factor / Q000235:genetics / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D050989:GATA2 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D020287:In Situ Nick-End Labeling; D008654:Mesothelioma; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D010997:Pleural Neoplasms; D034622:RNA Interference; D043684:Receptor, Adenosine A3 / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C494829:AIFM1 protein, human; C462504:ferroptosis suppressor protein 1, human; D058916:Adenosine A1 Receptor Antagonists; D058917:Adenosine A2 Receptor Antagonists; D058918:Adenosine A3 Receptor Antagonists; D051033:Apoptosis Inducing Factor; D051017:Apoptosis Regulatory Proteins; D050989:GATA2 Transcription Factor; C494711:GATA2 protein, human; D024101:Mitochondrial Proteins; D043684:Receptor, Adenosine A3; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D000249:Adenosine Monophosphate; D020169:Caspases; D000241:Adenosine