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A3 adenosine receptor-mediated p53-dependent apoptosis in Lu-65 human lung cancer cells

Tai-ichiro Otsuki1, Takeshi Kanno, Yumiko Fujita

  • 1Division of Bioinformation, Department of Physiology, Hyogo College of Medicine, Nishinomiya, Japan.

Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology
|July 5, 2012
PubMed
Abstract

Insights

Adenosine induces apoptosis in human giant cell lung carcinoma cells by upregulating p53 and Noxa via the A(3) adenosine receptor. This process activates caspase-9 and caspase-3, leading to programmed cell death.

Area of Science:

  • Molecular biology
  • Cancer research
  • Cell signaling

Background:

  • The A(3) adenosine receptor plays a role in cancer cell apoptosis through various signaling pathways.
  • Investigating the specific mechanisms of A(3) adenosine receptor-mediated apoptosis in Lu-65 cells, a human giant cell lung carcinoma line.

Purpose of the Study:

  • To elucidate the role of the A(3) adenosine receptor in adenosine-induced apoptosis in Lu-65 cells.
  • To identify the key molecular players, including p53 and caspase activation, involved in this process.

Main Methods:

  • Utilized MTT assays and TUNEL staining to assess cell viability and apoptosis.
  • Employed real-time RT-PCR and Western blotting to analyze gene and protein expression.
  • Investigated caspase-3, -8, and -9 activities and performed siRNA-mediated knockdown of A(3) adenosine receptor and p53.

Main Results:

  • Adenosine induced concentration-dependent apoptosis in Lu-65 cells, inhibited by A(3) receptor antagonist MRS1191 or knockdown of A(3) receptor/p53.
  • Adenosine and A(3) receptor agonist 2-Cl-IB-MECA triggered apoptosis.
  • Adenosine upregulated p53 and Noxa mRNA, activated caspase-3 and -9, effects dependent on A(3) receptor and p53.

Conclusions:

  • Adenosine upregulates p53 expression through the A(3) adenosine receptor.
  • This leads to p53-dependent Noxa gene transcription.
  • Activation of caspase-9 and caspase-3 subsequently induces apoptosis in Lu-65 cells.

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