Antiproliferative activity of 3-aminobenzamide in A431 carcinoma cells is associated with a target effect on cytoskeleton.
3-Aminobenzamide (3-ABA) is an inhibitor of poly(ADP-ribose)polymerase (PARP), an enzyme involved in several cellular processes, and exerts its effects by acting at the cytoskeleton level. Here we show that 3-ABA has an antiproliferative effect on the human carcinoma cell line A431, as measured by different assays. 3-ABA was capable of inhibiting cell growth as well as colony formation, this inhibitory effect is reversible. Morphological analyses showed a series of cellular alterations, such as a remarkable increase of dendritic-like protrusions, quite unusual in epithelial cells, and suggestive of a differentiative triggering. Immunocytochemical studies suggested that a major target of 3-ABA was indeed the cytoskeleton. These data, together with those of the literature, indicate that 3-ABA, depending on cell histotype and drug concentration, is a versatile drug capable of exerting antiproliferative and cytostatic effects as well as cytotoxic and antiapoptotic effects, processes sharing an important involvement of cytoskeleton. These unique characteristics of 3-ABA may be of interest for cancer research.
Tiozzo
R
R
Department of Biomedical Science, University of Modena, Italy.
Monti
D
D
Straface
E
E
Capri
M
M
Croce
M A
MA
Rainaldi
G
G
Franceschi
C
C
Malorni
W
W
D000199:Actins / Q000378:metabolism; D001549:Benzamides / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D014404:Tubulin / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000199:Actins; D001549:Benzamides; D004791:Enzyme Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D014404:Tubulin; C025160:3-aminobenzamide