Abstract
Purpose: To determine the effect of three calmodulin antagonists (A-7, W-7 and W-13) on the subpopulations of CD44/CD24 immunophenotypes in MDA-MB-231 and MDA-MB-468 breast cancer cell lines.
Methods: Flow cytometry analysis was used to determine the proportion of the various subpopulations of the immunophenotypes, viz, CD44+ CD24-, CD44-CD24+ and CD44+ CD24+, when MDA-MB-231 and MDA-MB-468 cells were subjected to calmodulin antagonists. The effect of W-13 on the invasion properties of MDA-MB-231 and MDA-MB-468 was investigated using Matrigel invasion assay.
Results: A-7, W-7 and W-13 caused alterations in the subpopulation of CD44+ CD24-in MDA-MB-231 cells. The most potent antagonist was W-13 as it reduced the proportion of tumorigenic CD44+ CD24-to 0.64 +/- 0.05 at a concentration of 80 mu M. In contrast, the subpopulation of MDA-MB-468 cells, which had a low fraction of CD44+ CD24-, was not altered when administered with W-7 but showed variations when incubated with W-13. Specifically, when the concentration of W-13 increased from 20 - 100 mu M, the proportion of CD44+ CD24+ was reduced from 92.93 +/- 3.2 to 60.96 +/- 2.4. The effect of W-13 on the subpopulations of CD44+ CD24-and CD44+ CD24+ in MDA-MB-231 and MDA-MB-468, respectively, reduced the invasion properties of the cells.
Conclusion: The calmodulin antagonist, W-13, has a significant antitumor effect on MDA-MB-231 and MDA-MB-468 breast cancer cells.