The involvement of protein kinase c (PKC) in the mechanism underlying the antimetastatic properties of triazenes was studied in C57BL/6 mice bearing Lewis lung carcinoma (3LL). In vivo and in vitro treatment with temozolomide, an in-vitro active analogue of dacarbazine, or calphostin c produced a concentration-dependent reduction of spontaneous and artificial metastases. Both agents reduced the ability of 3LL cells to adhere to endothelium. Diethylaminoethyl (DEAE)-sepharose chromatography of cell extracts revealed that incubation of 3LL cells with 12-0-tetradecanoylphorbol-13-acetate (TPA) caused a rapid translocation of protein kinase c activity from cytosol to the membrane fraction. Membrane PKC activity induced by TPA was reduced by 60% after treatment with temozolomide. Coincident with these changes, TPA induced phosphorylation of alpha-6 integrin, whereas temozolomide or calphostin c abolished the appearance of this phosphoprotein. These results suggest that temozolomide reduced metastatic potential by interfering with alpha-6 phosphorylation induced by PKC activation.

Tentori, L., Leonetti, C., Aquino, A. (1995). Temozolomide reduces the metastatic potential of Lewis-lung-carcinoma (3ll) in mice: role of alpha-6 integrin phosphorylation. EUROPEAN JOURNAL OF CANCER, 31A(5), 746-754 [10.1016/0959-8049(94)00521-6].

Temozolomide reduces the metastatic potential of Lewis-lung-carcinoma (3ll) in mice: role of alpha-6 integrin phosphorylation

TENTORI, LUCIO;AQUINO, ANGELO
1995-01-01

Abstract

The involvement of protein kinase c (PKC) in the mechanism underlying the antimetastatic properties of triazenes was studied in C57BL/6 mice bearing Lewis lung carcinoma (3LL). In vivo and in vitro treatment with temozolomide, an in-vitro active analogue of dacarbazine, or calphostin c produced a concentration-dependent reduction of spontaneous and artificial metastases. Both agents reduced the ability of 3LL cells to adhere to endothelium. Diethylaminoethyl (DEAE)-sepharose chromatography of cell extracts revealed that incubation of 3LL cells with 12-0-tetradecanoylphorbol-13-acetate (TPA) caused a rapid translocation of protein kinase c activity from cytosol to the membrane fraction. Membrane PKC activity induced by TPA was reduced by 60% after treatment with temozolomide. Coincident with these changes, TPA induced phosphorylation of alpha-6 integrin, whereas temozolomide or calphostin c abolished the appearance of this phosphoprotein. These results suggest that temozolomide reduced metastatic potential by interfering with alpha-6 phosphorylation induced by PKC activation.
1995
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/14 - FARMACOLOGIA
English
Con Impact Factor ISI
calphostin c; cell adhesion; integrins; metastasis; phosphorylation; PKC; temozolomide
Tentori, L., Leonetti, C., Aquino, A. (1995). Temozolomide reduces the metastatic potential of Lewis-lung-carcinoma (3ll) in mice: role of alpha-6 integrin phosphorylation. EUROPEAN JOURNAL OF CANCER, 31A(5), 746-754 [10.1016/0959-8049(94)00521-6].
Tentori, L; Leonetti, C; Aquino, A
Articolo su rivista
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/52874
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