Calmidazolium chloride (CMZ) is widely used as a calmodulin (CaM) antagonist, but is also known to induce apoptosis in certain cancer cell lines. However, in spite of the importance of cancer stem cells (CSCs) in cancer therapy, the effects of CMZ on CSCs are not yet well understood. We investigated the effects of CMZ on the F9 embryonal carcinoma cell (ECC) line as a surrogate model of CSCs. To avoid bias due to culture conditions, F9 ECCs and E14 embryonic stem cells (ESCs) were grown in the same culture medium. Results obtained using a cell-counting kit showed that CMZ significantly inhibited growth in F9 ECCs compared with growth in E14 ESCs. CMZ also induced apoptosis of F9 ECCs, but not of E14 ESCs, which was associated with caspase-3 activation and an increased fraction of the sub-G1 cell population. In addition, our data revealed that the expression of stemness-related genes including c-Myc was selectively down regulated in CMZ-treated F9 ECCs. Our results suggest that CMZ can inhibit the growth of ECCs by inducing apoptosis and down regulating stemness-related genes, without causing any harm to normal stem cells. These findings indicate a potential application of CMZ in the development of anti-CSC therapeutics.
Bibliographical noteFunding Information:
This work was supported in part by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) [No. 2011-0030049 ] and partly by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education [ NRF-2013R1A1A2007944 ]. In addition, this work was supported in part by Brain Korea 21(BK21) PLUS program. J. L., M. S.·K., M. A. K. are fellowship awarded by BK21 PLUS program.
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