Adenosine uptake is the major effector of extracellular ATP toxicity in human cervical cancer cells.
Bottom Line: Corroborating these data, blockage or knockdown of P2 × 7 only slightly reduced ATP cytotoxicity.Moreover, ATP-induced apoptosis and signaling-p53 increase, AMPK activation, and PARP cleavage-as well as autophagy induction were also inhibited by dipyridamole.In addition, inhibition of adenosine conversion into AMP also blocked cell death, indicating that metabolization of intracellular adenosine originating from extracellular ATP is responsible for the main effects of the latter in human cervical cancer cells.
Affiliation: Laboratory of Biochemical and Cytological Analysis, Faculty of Pharmacy, Federal University of Rio Grande do Sul, Porto Alegre, RS 90610-000, Brazil.Show MeSH
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Mentions: This relatively small contribution of P2×7 to cell death was confirmed with the use of a P2×7 antagonist, oxidized ATP (oATP), which only partially prevented the effect of ATP (Figure 4A). To reinforce these findings, P2×7 knockdown (KD) SiHa cells (Figure 4B) were slightly more resistant to ATP than were wild-type (WT) or KD control cells (Figure 4C), confirming the partial role of this receptor in the cytotoxic effect of ATP.
Affiliation: Laboratory of Biochemical and Cytological Analysis, Faculty of Pharmacy, Federal University of Rio Grande do Sul, Porto Alegre, RS 90610-000, Brazil.