In vivo modification of adriamycin-induced apoptosis in L-5178Y lymphoma cell-bearing mice by (+)-α-tocopherol and superoxide dismutase

Bravo-Cuellar, A.; Gómez-Contreras, P.C.; Lerma-Díaz, J.M.; Hernández-Flores, G.; Domínguez-Rodríguez, J.R.; Ortíz-Lazareno, P.; Cervantes-Munguia, R.; Orbach-Arbouys, S.

doi:10.1016/j.canlet.2005.01.013

« Previous Next »Cancer Letters
Volume 229, Issue 1 , Pages 59-65, 8 November 2005

In vivo modification of adriamycin-induced apoptosis in L-5178Y lymphoma cell-bearing mice by (+)-α-tocopherol and superoxide dismutase

A. Bravo-Cuellar
- CUALTOS, Universidad de Guadalajara, Guadalajara, Jal. México
- Corresponding author. Address: Centro de Investigación Biomédica de Occidente, IMSS, Sierra Mojada 800, Col. Independencia, CP 44340, Guadalajara, Jal. México. Tel.: +52 36 36189410; fax: +52 36 36181756.
P.C. Gómez-Contreras
- Centro de Investigación Biomédica de Occidente, IMSS Guadalajara, Jal. México
J.M. Lerma-Díaz
- Centro de Investigación Biomédica de Occidente, IMSS Guadalajara, Jal. México
G. Hernández-Flores
- Centro de Investigación Biomédica de Occidente, IMSS Guadalajara, Jal. México
J.R. Domínguez-Rodríguez
- Centro de Investigación Biomédica de Occidente, IMSS Guadalajara, Jal. México
P. Ortíz-Lazareno
- Centro de Investigación Biomédica de Occidente, IMSS Guadalajara, Jal. México
R. Cervantes-Munguia
- CUALTOS, Universidad de Guadalajara, Guadalajara, Jal. México
S. Orbach-Arbouys
- Service de Pharmacie, Hôpital Paul-Brousse, Villejuif, France

Received 23 December 2004; received in revised form 10 January 2005; accepted 17 January 2005.

Abstract

Apoptosis was followed in L5178Y lymphoma cell-bearing mice at different times after intraperitoneal injections of adriamycin (ADM). Apoptosis was determined morphologically and confirmed by DNA laddering on electrophoresis. Apoptosis was observed 36h after injection of 5mg/kg ADM (apoptotic cell index 64.2±5.6 vs. 1.5±2.1 from the untreated group) and confirmed by DNA electrophoresis. However, when the animals were pretreated with (+)-α-tocopherol acid succinate or superoxide dismutase before ADM administration apoptotic index significantly diminished (P<0.05) and the DNA electrophoresis did not show fragmentations. We conclude that in ADM-treated mice, tumour cell death occurs in two ways: first by necrosis, then later by apoptosis. These observations are likely to be associated with or caused by the generation of reactive oxygen species.