Publisher: Pharmacotherapy Group

Effect of Three Calmodulin Antagonists On Subpopulations of Cd44/Cd24 Immunophenotypes In Breast Cancer Cell Lines

Abdulwahab Noor Wali, Mohammed Farouk El Shal, Laila A Damiati, Mayson H Alkhatib
KEYWORDS: Calmodulin antagonists; Flow cytometry; Invasion assay; Immunophenotypes

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 μM. 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 μM, 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 cells. calmodulin antagonist, W-13, has a significant antitumor effect on MDA-MB-231 and MDA-MB-468 breast cancer


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