Anticancer effect of adenosine on gastric cancer via diverse signaling pathways.
Extracellular adenosine induces apoptosis in a variety of cancer cells via intrinsic and extrinsic pathways. In the former pathway, adenosine uptake into cells triggers apoptosis, and in the latter pathway, adenosine receptors mediate apoptosis. Extracellular adenosine also induces apoptosis of gastric cancer cells. Extracellular adenosine is transported into cells through an adenosine transporter and converted to AMP by adenosine kinase. In turn, AMP activates AMP-activated protein kinase (AMPK). AMPK is the factor responsible for caspase-independent apoptosis of GT3-TKB gastric cancer cells. Extracellular adenosine, on the other hand, induces caspase-dependent apoptosis of MKN28 and MKN45 gastric cancer cells by two mechanisms. Firstly, AMP, converted from intracellularly transported adenosine, initiates apoptosis, regardless of AMPK. Secondly, the A3 adenosine receptor, linked to Gi/Gq proteins, mediates apoptosis by activating the Gq protein effector, phospholipase Cγ, to produce inositol 1,4,5-trisphosphate and diacylglycerol, which activate protein kinase C. Consequently, the mechanisms underlying adenosine-induced apoptosis vary, depending upon gastric cancer cell types. Understand the contribution of each downstream target molecule of adenosine to apoptosis induction may aid the establishment of tailor-made chemotherapy for gastric cancer.
Ayako Tsuchiya, Tomoyuki Nishizaki, Division of Bioinformation, Department of Physiology, Hyogo College of Medicine, Nishinomiya 663-8501, Japan.
Ayako
A
Tsuchiya
Ayako Tsuchiya, Tomoyuki Nishizaki, Division of Bioinformation, Department of Physiology, Hyogo College of Medicine, Nishinomiya 663-8501, Japan.
Tomoyuki
T
Nishizaki
D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000241:Adenosine / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D000249:Adenosine Monophosphate / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D015398:Signal Transduction / Q000187:drug effects; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D000249:Adenosine Monophosphate; D055372:AMP-Activated Protein Kinases; D000241:Adenosine
Adenosine; Apoptosis; Extrinsic pathway; Gastric cancer; Intrinsic pathway