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Inhibition of melanoma cell/matrix interaction by tamoxifen.
- Source :
-
Melanoma research [Melanoma Res] 1993 Feb; Vol. 3 (1), pp. 67-74. - Publication Year :
- 1993
-
Abstract
- Following our recent finding that calmodulin antagonists can reduce cancer cell attachment to extracellular matrix proteins, we investigated the calmodulin antagonistic and anti-attachment properties of the non-steroidal anti-oestrogens tamoxifen and droloxifene. These drugs and four of their active metabolites were found to have calmodulin antagonist activity with IC50 values of 2-4 microM and to be capable of inhibiting attachment of murine B16 melanoma to extracellular matrix proteins in vitro. IC50 values for inhibition of attachment were 11 microM for tamoxifen and ranged from 5 to 40 microM for the other five compounds tested. (Poor reproducibility in drug potency between attachment experiments was almost certainly due to the low aqueous solubility of these drugs.) The effects of tamoxifen on cell/matrix adhesion were most evident between 15 min and 3 h of cell attachment. No effects of tamoxifen were evident in cells which had been allowed to attach for 6 h or more. Tamoxifen at concentrations between 0.1 and 30 microM was without effect on intracellular free calcium concentration. Tamoxifen also inhibited attachment of human ocular melanoma cells and human breast cancer (MCF7) cells to type I collagen. The concentration at which tamoxifen and its metabolites affect cell attachment in vitro (2-14 microM) is of the same order as the tissue concentrations of these drugs achieved clinically. The possibility exists that reduction of cell/matrix interactions may contribute to the clinical anti-metastatic efficacy of tamoxifen and some of its active metabolites.
- Subjects :
- Animals
Breast Neoplasms
Calmodulin antagonists & inhibitors
Collagen
Eye Neoplasms pathology
Female
Fibronectins
Humans
Laminin
Melanoma pathology
Mice
Structure-Activity Relationship
Tamoxifen metabolism
Tumor Cells, Cultured
Cell Adhesion drug effects
Estrogen Antagonists pharmacology
Extracellular Matrix Proteins
Eye Neoplasms physiopathology
Melanoma physiopathology
Melanoma, Experimental physiopathology
Tamoxifen analogs & derivatives
Tamoxifen pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0960-8931
- Volume :
- 3
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Melanoma research
- Publication Type :
- Academic Journal
- Accession number :
- 8471839
- Full Text :
- https://doi.org/10.1097/00008390-199304000-00010