The hEag1 K+ Channel Inhibitor Astemizole Stimulates Ca2+ Deposition in SaOS-2 and MG-63 Osteosarcoma Cultures

The hEag1 (Kv10.1) K+ channel is normally found in the brain, but it is ectopically expressed in tumor cells, including osteosarcoma. Based on the pivotal role of ion channels in osteogenesis, we tested whether pharmacological modulation of hEag1 may affect osteogenic differentiation of osteosarcoma...

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Published in:International journal of molecular sciences 2022-09, Vol.23 (18), p.10533
Main Authors: Mészáros, Beáta, Csoti, Agota, Szanto, Tibor G., Telek, Andrea, Kovács, Katalin, Toth, Agnes, Volkó, Julianna, Panyi, Gyorgy
Format: Article
Language:English
Subjects:
Assaying
Bone cancer
Calcium
Calcium ions
Cell cycle
Cell differentiation
Cytotoxicity
Deposition
Differentiation (biology)
Electrophysiology
Experiments
Gene expression
Ion channels
Medical prognosis
Mineralization
Molecular biology
Osteogenesis
Osteosarcoma
Osteosarcoma cells
Pharmacology
Potassium channels (voltage-gated)
Sarcoma
Sensitivity
Tumor cells
Tumors
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Summary:The hEag1 (Kv10.1) K+ channel is normally found in the brain, but it is ectopically expressed in tumor cells, including osteosarcoma. Based on the pivotal role of ion channels in osteogenesis, we tested whether pharmacological modulation of hEag1 may affect osteogenic differentiation of osteosarcoma cell lines. Using molecular biology (RT-PCR), electrophysiology (patch-clamp) and pharmacology (astemizole sensitivity, IC50 = 0.135 μM) we demonstrated that SaOS-2 osteosarcoma cells also express hEag1 channels. SaOS-2 cells also express to KCa1.1 K+ channels as shown by mRNA expression and paxilline sensitivity of the current. The inhibition of hEag1 (2 μM astemizole) or KCa1.1 (1 mM TEA) alone did not induce Ca2+ deposition in SaOS-2 cultures, however, these inhibitors, at identical concentrations, increased Ca2+ deposition evoked by the classical or pathological (inorganic phosphate, Pi) induction pathway without causing cytotoxicity, as reported by three completer assays (LDH release, MTT assay and SRB protein assay). We observed a similar effect of astemizole on Ca2+ deposition in MG-63 osteosarcoma cultures as well. We propose that the increase in the osteogenic stimuli-induced mineral matrix formation of osteosarcoma cell lines by inhibiting hEag1 may be a useful tool to drive terminal differentiation of osteosarcoma.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms231810533