TY - JOUR

T1 - Comparative Evaluation of Cardiotonic Steroid Action on the Viability of Differentiated and Undifferentiated Human Neuroblastoma SH-SY5Y Cell Culture

AU - Lopachev, A. V.

AU - Kazanskaya, R. B.

AU - Khutorova, A. V.

AU - Abaimov, D. A.

AU - Timoshina, Y. A.

AU - Fedorova, T. N.

PY - 2021/12

Y1 - 2021/12

N2 - Neuroblastoma (NB) is one of the most common childhood cancers. While it affects adults far lessfrequently than children, the prognosis for adults is significantly poorer. CTS, which are specific inhibitorsof the Na+,K+-ATPase, are known to be cytotoxic to cancer cells. However, the mechanisms behind their differential effect on cancerous and mature cells are poorly understood. We used the SH-SY5Y NB culture toinvestigate these effects. We showed that the CTS ouabain, digoxin, and bufalin are toxic for both undifferentiated and differentiated SH-SY5Y neuroblastoma in the concentration range of 10–100 nM. Digoxin at aconcentration of 100 nM, bufalin at a concentration of 10 nM. However, ouabain was an order of magnitudemore toxic for the undifferentiated (10 nM) culture than for the differentiated (100 nM) culture. It was alsoshown that differentiation of SH-SY5Y neuroblastoma using retinoic acid causes a manifold increase indopamine secreted by the culture into the culture medium. At the same time, ouabain causes a decrease inthe amount of dopamine secreted by both undifferentiated and differentiated SH-SY5Y neuroblastoma. Thetoxic effect of ouabain in undifferentiated culture is associated with a decrease in the amount of anti-apoptotic protein Bcl-2. It was also shown that the toxic effect of ouabain on the undifferentiated culture of SHSY5Y neuroblastoma is associated with PKC activity, since the addition of the PKC inhibitor chelerythrineneutralized the toxic effect of 10 nM ouabain. In all, our data suggests that CTS are important for futureinvestigation of the differential effect of anticancer compounds on dividing cells and mature neurons.

AB - Neuroblastoma (NB) is one of the most common childhood cancers. While it affects adults far lessfrequently than children, the prognosis for adults is significantly poorer. CTS, which are specific inhibitorsof the Na+,K+-ATPase, are known to be cytotoxic to cancer cells. However, the mechanisms behind their differential effect on cancerous and mature cells are poorly understood. We used the SH-SY5Y NB culture toinvestigate these effects. We showed that the CTS ouabain, digoxin, and bufalin are toxic for both undifferentiated and differentiated SH-SY5Y neuroblastoma in the concentration range of 10–100 nM. Digoxin at aconcentration of 100 nM, bufalin at a concentration of 10 nM. However, ouabain was an order of magnitudemore toxic for the undifferentiated (10 nM) culture than for the differentiated (100 nM) culture. It was alsoshown that differentiation of SH-SY5Y neuroblastoma using retinoic acid causes a manifold increase indopamine secreted by the culture into the culture medium. At the same time, ouabain causes a decrease inthe amount of dopamine secreted by both undifferentiated and differentiated SH-SY5Y neuroblastoma. Thetoxic effect of ouabain in undifferentiated culture is associated with a decrease in the amount of anti-apoptotic protein Bcl-2. It was also shown that the toxic effect of ouabain on the undifferentiated culture of SHSY5Y neuroblastoma is associated with PKC activity, since the addition of the PKC inhibitor chelerythrineneutralized the toxic effect of 10 nM ouabain. In all, our data suggests that CTS are important for futureinvestigation of the differential effect of anticancer compounds on dividing cells and mature neurons.

M3 - Article

VL - 47

SP - 859

EP - 866

JO - Human Physiology

JF - Human Physiology

SN - 0362-1197

IS - 8

ER -