Resveratrol (RES) is a natural occurring phytoalexin that has been shown to have chemopreventive activity. Resveratrol acts both by suppressing cell proliferation and inducing apoptosis in a variety of cancer cell lines. In this study, we show that RES induces apoptosis in MOLT-4 acute lymphoblastic leukaemia cells by modulating three different pathways that regulate cells survival and cell death. We show for the first time that RES inhibits the survival signalling pathways Notch and their down stream effector and modulates the operation of interacting signalling systems. It induces an increase in the levels of the pro-apoptotic proteins p53, its effector p21waf and Bax. We also show that RES inhibits the PI3K/Akt pathway and activates Gsk-3β. The data presented here demonstrate unequivocally that RES induces apoptosis by inhibiting the Notch pathway and markedly influencing the operation of the interacting apoptosis pathways mediated by p53 and PI3K/Akt. These data support findings from other laboratories that have suggested the use of RES as a chemopreventive agent. Here, we have identified potential signalling pathways influenced by RES and this could lead to the identification of the targets of RES-induced apoptosis and growth control.

Resveratrol-induced apoptosis in human T-cell acute lymphoblastic leukaemia MOLT-4 cells / V. Cecchinato, R. Chiaramonte, M. Nizzardo, B. Cristofaro, A. Basile, G.V. Sherbet, P.Comi. - In: BIOCHEMICAL PHARMACOLOGY. - ISSN 0006-2952. - 74:11(2007), pp. 1568-1574.

Resveratrol-induced apoptosis in human T-cell acute lymphoblastic leukaemia MOLT-4 cells

V. Cecchinato
Primo
;
R. Chiaramonte
Secondo
;
M. Nizzardo;A. Basile;P.Comi
Ultimo
2007

Abstract

Resveratrol (RES) is a natural occurring phytoalexin that has been shown to have chemopreventive activity. Resveratrol acts both by suppressing cell proliferation and inducing apoptosis in a variety of cancer cell lines. In this study, we show that RES induces apoptosis in MOLT-4 acute lymphoblastic leukaemia cells by modulating three different pathways that regulate cells survival and cell death. We show for the first time that RES inhibits the survival signalling pathways Notch and their down stream effector and modulates the operation of interacting signalling systems. It induces an increase in the levels of the pro-apoptotic proteins p53, its effector p21waf and Bax. We also show that RES inhibits the PI3K/Akt pathway and activates Gsk-3β. The data presented here demonstrate unequivocally that RES induces apoptosis by inhibiting the Notch pathway and markedly influencing the operation of the interacting apoptosis pathways mediated by p53 and PI3K/Akt. These data support findings from other laboratories that have suggested the use of RES as a chemopreventive agent. Here, we have identified potential signalling pathways influenced by RES and this could lead to the identification of the targets of RES-induced apoptosis and growth control.
Acute lymphoblastic leukemia; Apoptosis; Bax; Gsk; p53; PI3K; Resveratrol
Settore MED/04 - Patologia Generale
Settore MED/46 - Scienze Tecniche di Medicina di Laboratorio
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/35986
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