Induction of apoptosis by the inhibitors of poly(ADP-ribose)polymerase in HeLa cells.
To investigate the role of poly(ADP-ribose)polymerase (PARP) in the physiological condition of cell growth, we studied the ability of PARP inhibitors to induce apoptosis. Benzamide (BA) and 4-amino-1,8-naphthalimide (NAP), two well-known inhibitors of PARP, treatment increased nuclear fragmentation and caspase-3 activity in HeLa (Human cervical cancer cell line) cells. The increase of cellular NAD(+) level was observed in HeLa cells treated with BA in comparison with untreated control cells. For unrevealing the specific PARP family member responsible for such induction of apoptosis we knocked down and over-expressed PARP-1 gene in HeLa cells. PARP-1 knock down cells were sensitive to BA induced nuclear fragmentation and caspase-3 activation while exogenous expression of PARP-1 rendered cells resistant to BA induced apoptosis. This result indicated that inhibition of PARP-1 resulted in induction of apoptosis.
Ghosh
Utpal
U
Department of Biochemistry & Biophysics, University of Kalyani, Kalyani 741235, India. utpal8ghosh@yahoo.co.in
Bhattacharyya
Nitai P
NP
D015057:1-Naphthylamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001549:Benzamides / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation; D006367:HeLa Cells / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D006801:Humans; D053644:Naphthalimides / Q000494:pharmacology*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism; D015363:Quinolones / Q000494:pharmacology*
D001549:Benzamides; D053644:Naphthalimides; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D015363:Quinolones; C086538:4-amino-1,8-naphthalimide; C037689:benzamide; D015057:1-Naphthylamine; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3