Staurosporine increases carcinoembryonic antigen expression in a human colon cancer cell line.
Staurosporine (ST), a protein kinase C inhibitor, was found to produce antitumor effects against C22.20, a clonal subline derived from colon cancer HT-29 line, selected for low expression of carcinoembryonic antigen (CEA). However, as assessed by FACS analysis using propidium iodide, no apoptosis or cell cycle alteration was found on day 3 after treatment of C22.20 cells with ST (1-100nM). Exposure of cells to graded concentrations of the drug (i.e., from 1 to 25nM) resulted in a concentration-dependent increase in the percentage of CEA positive cells, as determined by flow cytometric analysis. However, when higher concentrations (i.e. 50nM - 100nM) of ST were used, the percentage of CEA positive cells declined compared to that detected in 25nM-treated tumor. Since these results were obtained in a clonal cell population, it is reasonable to hypothesize that induction rather than selection mechanism is involved in this phenomenon. The potential clinical interest of the present findings stems from the consideration that treatment with ST or its derivatives could improve sensitivity and efficacy of diagnostic and/or immunotherapeutic approaches based on CEA molecules.
Aquino
A
A
Department of Neuroscience, Section of Pharmacology and Medical Oncology, University of Rome Tor Vergata, Italy. Angelo.Aquino@UniRoma2.it
Prete
S P
SP
Baier
S
S
Cappelletti
D
D
Greiner
J W
JW
De Vecchis
L
L
Graziani
G
G
Bonmassar
E
E
D017209:Apoptosis; D002272:Carcinoembryonic Antigen / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics; D002453:Cell Cycle / Q000187:drug effects; D003110:Colonic Neoplasms / Q000276:immunology / Q000473:pathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D019073:HT29 Cells / Q000187:drug effects / Q000276:immunology; D006801:Humans; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D019311:Staurosporine / Q000494:pharmacology*
D002272:Carcinoembryonic Antigen; D004791:Enzyme Inhibitors; D011493:Protein Kinase C; D019311:Staurosporine