Cell cycle arrest and the induction of apoptosis in pancreatic cancer cells exposed to adenosine triphosphate in vitro.
Adenosine triphosphate (ATP) has been shown to be an inhibitory or a stimulatory agent for cell growth in various types of cells. Here, we studied the effects of extracellular ATP on two pancreatic cancer cell lines, PK-1 and YAPC established by us. In both cell lines, ATP inhibited cell growth in a time- and dose-dependent manner, whereas the same doses of ATP stimulated DNA synthesis. Flow cytometric analysis of the cells incubated with or without ATP demonstrated the ATP-induced striking increase in cells at S-phase. The same analysis showed also the increase in sub-G0/G1 population in the same analysis and the electrophoretic pattern of DNA showed the occurrence of ATP-induced cell disintegration likely to be apoptosis. We suggest that extracellular ATP is cytotoxic for pancreatic cancer cells because of its induction of cell cycle arrest at S-phase and cell death, possibly apoptosis, overcoming the promotion of the entry into S-phase.
Yamada
Takayuki
T
Second Department of Surgery, Gunma University, Showamachi, Gunma 371-8511, Japan. yamadat@showa.gunma-u.ac.jp
Okajima
Fumikazu
F
Akbar
Mohammed
M
Tomura
Hideaki
H
Narita
Torao
T
Yamada
Tatsuya
T
Ohwada
Susumu
S
Morishita
Yasuo
Y
Kondo
Yoichi
Y
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D004273:DNA, Neoplasm / Q000187:drug effects; D005434:Flow Cytometry; D005562:Formazans; D006801:Humans; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013778:Tetrazolium Salts; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects
D004273:DNA, Neoplasm; D005562:Formazans; D013778:Tetrazolium Salts; C079782:MTT formazan; D000255:Adenosine Triphosphate; D013936:Thymidine