Cell death protection by 3-aminobenzamide: impairment of cytoskeleton function in human NK cell-mediated killing.
3-aminobenzamide, an inhibitor of the nuclear enzyme poly(ADP-ribose) polymerase, is capable of interfering with the tumor cell lysis induced by specialized cells from the immune system, i.e., natural killer (NK) cells. In this report we suggest that the mechanism by which the drug can exert its protective effects on target cell killing by NK effectors can also be due to its ability to impair cell-to-cell conjugate formation (binding), without affecting either the expression of cell adhesion molecules nor the features of effector-target cell contact. The mechanism of this inhibition seems to be associated with an alteration of cytoskeletal elements involved during conjugate formation, i.e., with the integrity and function of the microfilament system.
Malorni
W
W
Department of Ultrastructures, Istituto Superiore di Sanità, Roma, Italy.
Rainaldi
G
G
Straface
E
E
Rivabene
R
R
Cossarizza
A
A
Salvioli
S
S
Monti
D
D
Franceschi
C
C
D008841:Actin Cytoskeleton / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D015703:Antigens, CD / Q000032:analysis / Q000096:biosynthesis; D001549:Benzamides / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects* / Q000276:immunology; D003599:Cytoskeleton / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008856:Microscopy, Fluorescence; D000067856:Poly(ADP-ribose) Polymerase Inhibitors
D015703:Antigens, CD; D001549:Benzamides; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C025160:3-aminobenzamide