Extracellular Guanosine and Guanine Nucleotides Decrease Viability of Human Breast Cancer SKBR-3 Cells.

Area of Science:

• Biochemistry
• Cell Biology
• Cancer Research

Background:

• Adenosine and adenine nucleotides' effects on cancer purinergic receptors are known.
• The impact of extracellular guanosine and guanine nucleotides on breast cancer cells is not well understood.

Purpose of the Study:

• To investigate the influence of extracellular guanosine and guanine nucleotides on human breast cancer SKBR-3 cells.
• To elucidate the mechanisms by which these compounds affect cancer cell viability, proliferation, and apoptosis.

Main Methods:

• Treatment of SKBR-3 cells with guanosine and guanine nucleotides.
• Assessment of cell viability, proliferation, mitochondrial reactive oxygen species (ROS) production, and cell cycle modification.
• Evaluation of the effects of adenosine, dipyridamole (ENT 1/2 inhibitor), and adenosine receptor agonists/antagonists on nucleotide-induced cell death.

Main Results:

• Extracellular guanosine and guanine nucleotides decreased SKBR-3 cell viability and proliferation.
• Nucleotide treatment increased mitochondrial ROS production and altered the cell cycle.
• Guanosine-induced cell death was inhibited by adenosine and dipyridamole, suggesting ENT1/2 inhibition, but not by adenosine receptor modulators.
• GTP-induced cell death was suppressed by adenosine, dipyridamole, and the A1 receptor agonist CCPA, indicating partial mediation via adenosine A1 receptor antagonism.

Conclusions:

• Both guanosine and GTP induce apoptosis in breast cancer cells.
• Guanosine and GTP appear to trigger apoptosis through at least partially different molecular mechanisms.
• Guanosine may inhibit adenosine uptake via ENT1/2, while GTP's effects involve partial antagonism of the adenosine A1 receptor.