Biological response modifiers, such as dibutyryl-cAMP (db-cAMP) and retinoic acid (RA) have been demonstrated to induce in vitro the reappearance of a differentiated phenotype in transformed cells (i.e.: neuroblastoma, myeloid leukaemia, teratoma cells, etc.), simultaneously decreasing cell proliferation rate. Treatment for 72 hours with db-cAMP (1mM) of a highly malignant human anaplastic thyroid carcinoma cell line (ARO) induced a marked reduction (- 44%) of cell proliferation , as measured by (3H)-thymidine uptake. No effect on cell proliferation rate was observed in the presence of RA (5uM), while the combination of RA and db-cAMP treatment showed results similar to those obtained with db-cAMP alone. The db-cAMP dependent inhibition of ARO cell proliferation, was confirmed by direct assessment of the number of mitotic cells. The expression of cell cycle-related genes, such as those coding for cyclins and cyclin-dependent kinases, was not modified after ARO cell treatment with either db-cAMP or RA, as shown by indirect immunofluorescence, Northern and Western blot analyses. Colony-forming ability of ARO cells in soft agar, was dramatically reduced by db-cAMP treatment but unmodified by RA. In conclusion, prolonged exposure to db-cAMP but not to RA treatment is able to inhibit the proliferation rate of ARO cells and to greatly reduce their tumorigenic potential in vitro.
INHIBITION OF PROLIFERATION AND TUMORIGENIC POTENTIAL OF HUMAN THYROID ANAPLASTIC CARCINOMA CELLS BY LONG-TERM EXPOSURE TO cAMP.
1995
Abstract
Biological response modifiers, such as dibutyryl-cAMP (db-cAMP) and retinoic acid (RA) have been demonstrated to induce in vitro the reappearance of a differentiated phenotype in transformed cells (i.e.: neuroblastoma, myeloid leukaemia, teratoma cells, etc.), simultaneously decreasing cell proliferation rate. Treatment for 72 hours with db-cAMP (1mM) of a highly malignant human anaplastic thyroid carcinoma cell line (ARO) induced a marked reduction (- 44%) of cell proliferation , as measured by (3H)-thymidine uptake. No effect on cell proliferation rate was observed in the presence of RA (5uM), while the combination of RA and db-cAMP treatment showed results similar to those obtained with db-cAMP alone. The db-cAMP dependent inhibition of ARO cell proliferation, was confirmed by direct assessment of the number of mitotic cells. The expression of cell cycle-related genes, such as those coding for cyclins and cyclin-dependent kinases, was not modified after ARO cell treatment with either db-cAMP or RA, as shown by indirect immunofluorescence, Northern and Western blot analyses. Colony-forming ability of ARO cells in soft agar, was dramatically reduced by db-cAMP treatment but unmodified by RA. In conclusion, prolonged exposure to db-cAMP but not to RA treatment is able to inhibit the proliferation rate of ARO cells and to greatly reduce their tumorigenic potential in vitro.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
