Preliminary studies, performed in our laboratory, showed that staurosporine (ST), a protein-kinase (PK) inhibitor, increases the expression of the carcinoembryonic antigen (CEA) in a human colon cancer cell line. The present study explores the cellular and molecular effects of ST on the CEA expression in breast cancer MCF-7 line and in a number of colon cancer cell lines characterized by the different basal levels of the antigen, including two cloned sublines (i.e. C22.20 and C6.6, expressing low and high CEA levels, respectively). In all cases, increase of the CEA expression was observed at drug concentrations devoid of marked cytostatic effects (e.g. 5 nM) and was accompanied by the enhanced CEA shedding in the supernatant. Moreover, the increase of the CEA levels both occurred in the cell membranes and in the cytosolic compartments and appeared to be the result of the enhanced CEA gene transcription. Similar results have been previously obtained with interferon-gamma. However, ST treatment, different from interferon-gamma, did not up-regulate the level of the HLA class I molecules. A preliminary investigation also showed that other PKC inhibitors did not substantially modulate the CEA expression. Therefore, the biochemical mechanism underlying the effect of ST should not be correlated with that involved in the PKC inhibition. The present study suggests that ST and, presumably, its analogs used in the cancer treatment could enhance the CEA expression on neoplastic cells in patients affected by the CEA-positive malignancies. This appears to be of potential clinical interest for the development of new immunotherapeutic or diagnostic approaches based on the pharmacological modulation of this antigenic marker.

Prete, S., Cappelletti, D., Baier, S., Nasuti, P., Guadagni, F., DE VECCHIS, L., et al. (2002). Pharmacological modulation of carcinoembryonic antigen in human cancer cells: studies with staurosporine. INTERNATIONAL IMMUNOPHARMACOLOGY, 2(5), 641-651.

Pharmacological modulation of carcinoembryonic antigen in human cancer cells: studies with staurosporine

PRETE, SALVATORE;DE VECCHIS, LIANA;BONMASSAR, ENZO;GRAZIANI, GRAZIA;AQUINO, ANGELO
2002-04-01

Abstract

Preliminary studies, performed in our laboratory, showed that staurosporine (ST), a protein-kinase (PK) inhibitor, increases the expression of the carcinoembryonic antigen (CEA) in a human colon cancer cell line. The present study explores the cellular and molecular effects of ST on the CEA expression in breast cancer MCF-7 line and in a number of colon cancer cell lines characterized by the different basal levels of the antigen, including two cloned sublines (i.e. C22.20 and C6.6, expressing low and high CEA levels, respectively). In all cases, increase of the CEA expression was observed at drug concentrations devoid of marked cytostatic effects (e.g. 5 nM) and was accompanied by the enhanced CEA shedding in the supernatant. Moreover, the increase of the CEA levels both occurred in the cell membranes and in the cytosolic compartments and appeared to be the result of the enhanced CEA gene transcription. Similar results have been previously obtained with interferon-gamma. However, ST treatment, different from interferon-gamma, did not up-regulate the level of the HLA class I molecules. A preliminary investigation also showed that other PKC inhibitors did not substantially modulate the CEA expression. Therefore, the biochemical mechanism underlying the effect of ST should not be correlated with that involved in the PKC inhibition. The present study suggests that ST and, presumably, its analogs used in the cancer treatment could enhance the CEA expression on neoplastic cells in patients affected by the CEA-positive malignancies. This appears to be of potential clinical interest for the development of new immunotherapeutic or diagnostic approaches based on the pharmacological modulation of this antigenic marker.
apr-2002
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/14 - FARMACOLOGIA
Settore MED/06 - ONCOLOGIA MEDICA
English
Con Impact Factor ISI
Carcinoembryonic Antigen; Tumor Cells, Cultured; Humans; Staurosporine; Cytosol; Cell Membrane; Gene Expression Regulation
Prete, S., Cappelletti, D., Baier, S., Nasuti, P., Guadagni, F., DE VECCHIS, L., et al. (2002). Pharmacological modulation of carcinoembryonic antigen in human cancer cells: studies with staurosporine. INTERNATIONAL IMMUNOPHARMACOLOGY, 2(5), 641-651.
Prete, S; Cappelletti, D; Baier, S; Nasuti, P; Guadagni, F; DE VECCHIS, L; Greiner, J; Bonmassar, E; Graziani, G; 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/2108/51743
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