In this study, we examined possible mechanisms of caspase activation during carotenoid-induced apoptosis in tumor cells. We found that beta-Carotene induces apoptosis by the activation of caspase-3 in human leukemia (HL-60), colon adenocarcinoma (HT-29) as well as melanoma (SK-MEL-2) cell lines. This activation is dose dependent and follows that of caspase-8 and caspase-9. Although caspase-8 cleavage is an early event, reaching its maximum activation at 3 h, caspase-9 reaches its maximum activation only at 6 h. The addition of IETD-CHO, a caspase-8-specific inhibitor, completely prevents beta-Carotene-induced apoptosis, whereas only a partial prevention was observed in the presence of LEHD-CHO, a caspase-9-specific inhibitor. beta-Carotene activates caspase-9 via cytochrome c release from mitochondria and loss of mitochondrial membrane potential (Dym). Concomitantly, a dose-dependent decrease in the antiapoptotic protein Bcl-2 and a dose-dependent increase in the cleaved form of BID (t-BID) are observed. Moreover, NF-kB activation is involved in beta-Carotene-induced caspase cascade. These results support a pharmacological role for beta-Carotene as a candidate antitumor agent and show a possible sequence of molecular events by which this molecule may induce apoptosis in tumor cells.

Palozza, P., Serini, S., Torsello, A., Di Nicuolo, F., Maggiano, N. G., Ranelletti, F. O., Wolf, F., Calviello, G., Mechanism of Activation of Caspase Cascade During beta-Carotene-InducedApoptosis in Human Tumor Cells, <<JOURNAL OF NUTRITION>>, 2003; (47): 76-87 [http://hdl.handle.net/10807/23765]

Mechanism of Activation of Caspase Cascade During beta-Carotene-Induced Apoptosis in Human Tumor Cells

Palozza, Paola;Serini, Simona;Torsello, Angela;Di Nicuolo, Fiorella;Maggiano, Nicola Giuseppe;Ranelletti, Franco Oreste;Wolf, Federica;Calviello, Gabriella
2003

Abstract

In this study, we examined possible mechanisms of caspase activation during carotenoid-induced apoptosis in tumor cells. We found that beta-Carotene induces apoptosis by the activation of caspase-3 in human leukemia (HL-60), colon adenocarcinoma (HT-29) as well as melanoma (SK-MEL-2) cell lines. This activation is dose dependent and follows that of caspase-8 and caspase-9. Although caspase-8 cleavage is an early event, reaching its maximum activation at 3 h, caspase-9 reaches its maximum activation only at 6 h. The addition of IETD-CHO, a caspase-8-specific inhibitor, completely prevents beta-Carotene-induced apoptosis, whereas only a partial prevention was observed in the presence of LEHD-CHO, a caspase-9-specific inhibitor. beta-Carotene activates caspase-9 via cytochrome c release from mitochondria and loss of mitochondrial membrane potential (Dym). Concomitantly, a dose-dependent decrease in the antiapoptotic protein Bcl-2 and a dose-dependent increase in the cleaved form of BID (t-BID) are observed. Moreover, NF-kB activation is involved in beta-Carotene-induced caspase cascade. These results support a pharmacological role for beta-Carotene as a candidate antitumor agent and show a possible sequence of molecular events by which this molecule may induce apoptosis in tumor cells.
Inglese
Palozza, P., Serini, S., Torsello, A., Di Nicuolo, F., Maggiano, N. G., Ranelletti, F. O., Wolf, F., Calviello, G., Mechanism of Activation of Caspase Cascade During beta-Carotene-InducedApoptosis in Human Tumor Cells, <<JOURNAL OF NUTRITION>>, 2003; (47): 76-87 [http://hdl.handle.net/10807/23765]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/23765
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