Abstract
Growing evidence suggests that breast cancer originates from a minor population of cancer cells termed cancer stem cells (CSCs), which can be identified by aldehyde dehydrogenase (ALDH) activity-based flow cytometry analysis. However, novel therapeutic drugs for the eradication of CSCs have not been discovered yet. Recently, drug repositioning, which finds new medical uses from existing drugs, has been expected to facilitate drug discovery. We have previously reported that sphingosine kinase 1 (SphK1) induced proliferation of breast CSCs. In the present study, we focused on the immunosuppressive agent FTY720 (also known as fingolimod or Gilenya), since FTY720 is known to be an inhibitor of SphK1. We found that FTY720 blocked both proliferation of ALDH-positive cells and formation of mammospheres. In addition, we showed that FTY720 reduced the expression of stem cell markers such as Oct3/4, Sox2 and Nanog via upregulation of protein phosphatase 2A (PP2A). These results suggest that FTY720 is an effective drug for breast CSCs in vitro.
Highlights
Since we have previously reported that sphingosine kinase 1 (SphK1) induced proliferation of breast cancer stem cells (CSCs) [13], we focused on the immunosuppressive agent FTY720, which is well known to be a SphK1 inhibitor and is used as immunosuppressive agents clinically
We investigated the effect of FTY720 on the proliferation of breast aldehyde dehydrogenase (ALDH)-positive cells from the MCF-7 cell line and MDA-MB-231 cell line
FTY720 inhibited mammosphere formation in both cell lines (Figure 1B). These results suggest that FTY720 is a potential effective drug for breast CSCs
Summary
Growing evidence suggests that many types of cancer including breast cancer are initiated from a small population of cancer stem cells (CSCs) [1,2,3,4,5,6,7,8]. This minor population produces the bulk of cancers through continuous self-renewal and differentiation, which contributes to cancer heterogeneity. CSCs have been considered to have similar properties to embryonic and normal adult stem cells [9]. Since CSCs are considered to have the abilities of a drug resistance and tumor recurrence initiation, novel therapeutic drugs for the eradication of CSCs have been required for cancer treatment
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