title: Calmidazolium chloride inhibits growth of murine embryonal carcinoma cells, a model of cancer stem-like cells.
abstract: 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.
authors.affiliation: Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea; Initiative for Biological Function & Systems, Yonsei University, Seoul 120-749, Republic of Korea.
authors.forename: Jina
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea; Initiative for Biological Function & Systems, Yonsei University, Seoul 120-749, Republic of Korea.
authors.forename: Min Seong
authors.initials: MS
authors.lastname: Kim
authors.affiliation: Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea; Initiative for Biological Function & Systems, Yonsei University, Seoul 120-749, Republic of Korea.
authors.forename: Min Aeh
authors.initials: MA
authors.lastname: Kim
authors.affiliation: Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea; Initiative for Biological Function & Systems, Yonsei University, Seoul 120-749, Republic of Korea. Electronic address: ykjang@yonsei.ac.kr.
authors.forename: Yeun Kyu
authors.initials: YK
authors.lastname: Jang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D053938:DNA Fragmentation; D015536:Down-Regulation; D054278:Embryonal Carcinoma Stem Cells / Q000187:drug effects* / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology*; D051379:Mice; D000071317:Nanog Homeobox Protein / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D055748:SOXB1 Transcription Factors / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; C489428:Myc protein, mouse; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; C031938:calmidazolium
keywords: Calmidazolium chloride; Cancer stem-like cells; Embryonal carcinoma cells; Growth inhibition