Selective permeabilization of cervical cancer cells to an ionic DNA-binding cytotoxin by activation of P2Y receptors.
Extracellular ATP is known to permeabilize certain cell types to polyatomic cations like YO-PRO1. Here, we report that extracellularly applied ATP stimulated rapid uptake and accumulation of an otherwise weakly membrane permeable fluorescent DNA-binding cytotoxin, Hoechst 33258, into cervical cancer cells. While ATP stimulated Hoechst 33258 uptake in 20-70% of cells from seven cervical cancer cell lines, it stimulated uptake in less than 8% of cervical epithelial cells obtained from the normal transformation zone and ectocervix tissue of 11 patients. ATP-evoked Hoechst 33258 uptake was independent of ionotropic P2X receptors, but dependent on activation of P2Y receptors. Thus, we show here that cervical cancer cells can be selectively induced to take up and accumulate an ionic cytotoxin by exposure to extracellular ATP.
Department of Biology, Clarkson University, 8 Clarkson Ave., Potsdam, NY 13699-5805, USA.
Maurish
M
Bukhari
Department of Biology, Clarkson University, 8 Clarkson Ave., Potsdam, NY 13699-5805, USA.
Han
H
Deng
Department of Biology, Clarkson University, 8 Clarkson Ave., Potsdam, NY 13699-5805, USA.
Noelle
N
Jones
Department of Biology, Clarkson University, 8 Clarkson Ave., Potsdam, NY 13699-5805, USA.
Zachary
Z
Towne
Department of Biology, Clarkson University, 8 Clarkson Ave., Potsdam, NY 13699-5805, USA.
Craig D
CD
Woodworth
Department of Biology, Clarkson University, 8 Clarkson Ave., Potsdam, NY 13699-5805, USA. Electronic address: dsamways@clarkson.edu.
Damien S K
DS
Samways
D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D001562:Benzimidazoles / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D003603:Cytotoxins / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D004273:DNA, Neoplasm / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008856:Microscopy, Fluorescence; D015394:Molecular Structure; D058912:Purinergic P2Y Receptor Agonists / Q000494:pharmacology; D058921:Purinergic P2Y Receptor Antagonists / Q000494:pharmacology; D058470:Receptors, Purinergic P2Y / Q000378:metabolism*; D014544:Uridine Triphosphate / Q000494:pharmacology; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology
D001562:Benzimidazoles; D003603:Cytotoxins; D004273:DNA, Neoplasm; C111914:N(6)-methyl-2'-deoxyadenosine 3',5'-diphosphate; D058912:Purinergic P2Y Receptor Agonists; D058921:Purinergic P2Y Receptor Antagonists; D058470:Receptors, Purinergic P2Y; C447680:hoechst 32258; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D002118:Calcium; D014544:Uridine Triphosphate
Ca(2+); Cervical cancer; Doxorubicin; Drug delivery; Hoechst 33258; P2X; P2Y; Permeability; Pibenzimol; Purinergic