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Cell Biology International (2011) 35, 783–788 (Printed in Great Britain)
Lidocaine-induced apoptosis of gingival fibroblasts: participation of cAMP and PKC activity
Emmanuel Quinteros Villarruel*, Enri Borda*†, Leonor Sterin‑Borda*† and Betina Orman*1
*Pharmacology Unit, School of Dentistry, University of Buenos Aires, Buenos Aires, Argentina, and †Argentine National Research Council CONICET, Buenos Aires, Argentina

Local anaesthetics are drugs that prevent or relieve pain by interrupting nervous conduction and are the most commonly used drugs in dentistry. Their main targets of action are voltage-dependent Na+ channels. The Na+ channel is modulated by phosphorylation of two enzymes: PKA (protein kinase A) and PKC (protein kinase C). We studied the ability of lidocaine to modulate programmed cell death of human gingival fibroblasts and the mechanisms involved in this process. Lidocaine (10−5 to 10−7 M) stimulated apoptosis in primary cultures and the caspase-3 activity in a concentration-dependent manner. The stimulatory effect of lidocaine on apoptosis was attenuated in the presence of HA 1004 (PKA inhibitor) and stimulated by staurosporine and Go 6976 (PKC inhibitors). Lidocaine-induced apoptotic nuclei correlated positively with cAMP accumulation and negatively with PKC activity. These results show that lidocaine promotes apoptosis in human gingival fibroblasts at concentrations used for local anaesthesia. The mechanism involves PKA stimulation and PKC inhibition, which in turn stimulates caspase-3 and leads to programmed cell death.

Key words: apoptosis, caspase-3, lidocaine, protein kinase A, protein kinase C

Abbreviations: db, dibutyril, PMA, phorbol 12-myristate-13-acetate, PKA, protein kinase A, PKC, protein kinase C, HA 1004, N-(2-guanidinoethyl)-5-isoquinolinesulfonamide, hydrochloride, TUNEL, terminal deoxynucleotidyltransferase-mediated dUTP nick-end labelling

1To whom correspondence should be addressed (email

Received 2 April 2010/18 August 2010; accepted 3 November 2010

Published as Cell Biology International Immediate Publication 3 November 2010, doi:10.1042/CBI20100200

© The Author(s) Journal compilation © 2011 Portland Press Limited

ISSN Print: 1065-6995
ISSN Electronic: 1095-8355
Published by Portland Press Limited on behalf of the International Federation for Cell Biology (IFCB)