In:
PLOS ONE, Public Library of Science (PLoS), Vol. 18, No. 6 ( 2023-6-30), p. e0287769-
Abstract:
Biliary tract cancer is a deadly disease with limited therapeutic options. Ouabain is a well-known inhibitor of the pumping function of Na + /K + -ATPase, though there is evidence that low concentrations of ouabain lead to a reduction of cell viability of cancer cells independent of its inhibition of the pumping function of the Na + /K + -ATPase. Regarding the impact of ouabain on biliary tract cancer, no data is currently available. Therefore, we aimed for a first-time investigation of ouabain as a potential anti-neoplastic biliary tract cancer agent using comprehensive human biliary tract cancer in vitro models. We found that ouabain has a strong cell line-dependent cytotoxic effect with IC 50 levels in the (low) nanomolar-range and that this effect was not associated with the mRNA expression levels of the Na + /K + -ATPase α , β and fxyd -subunits. Regarding the mode of cytotoxicity, we observed induction of apoptosis in biliary tract cancer cells upon treatment with ouabain. Interestingly, cytotoxic effects of ouabain at sub-saturating ( 〈 μM) levels were independent of cellular membrane depolarization and changes in intracellular sodium levels. Furthermore, using a 3D cell culture model, we found that ouabain disturbs spheroid growth and reduces the viability of biliary tract cancer cells within the tumor spheroids. In summary, our data suggest that ouabain possesses anti-biliary tract cancer potential at low μM-concentration in 2D and 3D in vitro biliary tract cancer models and encourage further detailed investigation.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0287769
DOI:
10.1371/journal.pone.0287769.g001
DOI:
10.1371/journal.pone.0287769.g002
DOI:
10.1371/journal.pone.0287769.g003
DOI:
10.1371/journal.pone.0287769.g004
DOI:
10.1371/journal.pone.0287769.g005
DOI:
10.1371/journal.pone.0287769.g006
DOI:
10.1371/journal.pone.0287769.s001
DOI:
10.1371/journal.pone.0287769.s002
DOI:
10.1371/journal.pone.0287769.s003
DOI:
10.1371/journal.pone.0287769.s004
DOI:
10.1371/journal.pone.0287769.s005
DOI:
10.1371/journal.pone.0287769.s006
DOI:
10.1371/journal.pone.0287769.s007
DOI:
10.1371/journal.pone.0287769.s008
DOI:
10.1371/journal.pone.0287769.s009
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2023
detail.hit.zdb_id:
2267670-3
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