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 mu M) 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 mu M 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.
