3-aminobenzamide, a potent inhibitor of poly (ADP-ribose) polymerase, causes a rapid death of HL-60 cells cultured in serum-free medium.
HL-60 cells transferred from serum-supplemented to serum-free culture medium initially bound to culture plate tightly and then released from the plate on increasing the culture time and resumed exponential growth after about 8 h lag. At the initial stage of the culture, the cells became extremely sensitive to 3-aminobenzamide, a potent inhibitor of poly (ADP-ribose) polymerase, and, at 1 mM, 80 to 90% of the cells were lysed within 20 h, whereas the inhibitor was totally ineffective on the cell growth in serum-supplemented medium at the concentration. Non-inhibitory analogs of the inhibitor were ineffective. Assay of poly(ADP-ribose) polymerase activity in permeable cells indicated that a transient activation of the enzyme occurred during the culture in serum-free medium (the maximum activation was observed at 8 h of the culture). The cells conditioned in serum-free medium for 24 h acquired significant resistancy to the inhibitor. A low concentration of fibronectin (5 to 10 micrograms/ml) and a relatively high concentration of bovine serum albumin (0.5 to 1 mg/ml) effectively blocked the cell attachment to plate and also the 3-aminobenzamide-induced cell lysis. These results suggest that poly(ADP-ribose) polymerase is involved in a process essential for HL-60 cells to adapt to a serum-deprived growth condition.
Department of Biochemistry, Nara Medical University, Japan.
K
K
Yoshihara
M
M
Tsuyuki
A
A
Itaya
Y
Y
Tanaka
T
T
Kamiya
D001549:Benzamides / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D016895:Culture Media, Serum-Free / Q000494:pharmacology*; D005353:Fibronectins / Q000494:pharmacology; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology*; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000187:drug effects
D001549:Benzamides; D016895:Culture Media, Serum-Free; D005353:Fibronectins; D009363:Neoplasm Proteins; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D012710:Serum Albumin, Bovine; C025160:3-aminobenzamide