Ouabain at nanomolar concentrations is cytotoxic for biliary tract cancer cells

被引:3
|
作者
Mayr, Christian [1 ,2 ]
Kiesslich, Tobias [1 ,2 ]
Bekric, Dino [1 ]
Beyreis, Marlena [1 ]
Kittl, Michael [1 ,6 ]
Ablinger, Celina [3 ]
Neureiter, Elen [1 ]
Pichler, Martin [4 ,5 ,6 ]
Prinz, Felix [4 ,5 ]
Ritter, Markus [1 ,7 ,8 ,9 ]
Neureiter, Daniel [10 ,11 ]
Jakab, Martin [1 ,7 ,8 ]
Dobias, Heidemarie [1 ]
机构
[1] Paracelsus Med Univ, Inst Physiol & Pathophysiol Salzburg, Ctr Physiol Pathophysiol & Biophys, Salzburg, Austria
[2] Paracelsus Med Univ, Univ Clin Salzburg, Dept Internal Med 1, Salzburg, Austria
[3] Paracelsus Med Univ, Inst Pharm, Salzburg, Austria
[4] Med Univ Graz, Dept Internal Med, Div Oncol, Graz, Austria
[5] Med Univ Graz, Res Unit Noncoding RNA & Genome Editing, Graz, Austria
[6] Univ Hosp Augsburg, Translat Oncol, Augsburg, Germany
[7] Paracelsus Med Univ, Ludwig Boltzmann Inst Arthrit & Rehabil, Salzburg, Austria
[8] Paracelsus Med Univ, Gastein Res Inst, Salzburg, Austria
[9] Kathmandu Univ, Sch Med Sci, Dhulikhel, Nepal
[10] Paracelsus Med Univ, Univ Clin Salzburg, Inst Pathol, Salzburg, Austria
[11] Canc Cluster Salzburg, Salzburg, Austria
来源
PLOS ONE | 2023年 / 18卷 / 06期
关键词
GROWTH-FACTOR RECEPTOR; NA+/K+-ATPASE; K+-ATPASE; CHOLANGIOCARCINOMA; APOPTOSIS; LINE; ESTABLISHMENT; SIGNAL; DEATH; SRC;
D O I
10.1371/journal.pone.0287769
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 IC50 levels in the (low) nanomolar-range and that this effect was not associated with the mRNA expression levels of the Na+/K+-ATPase & alpha;, & beta; 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 (< & mu;M) 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 & mu;M-concentration in 2D and 3D in vitro biliary tract cancer models and encourage further detailed investigation.
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页数:19
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