Publication

SK channel activation potentiates auranofin-induced cell death in glio- and neuroblastoma cells

Krabbendam, I. E., Honrath, B., Bothof, L., Silva-Pavez, E., Huerta, H., Peñaranda Fajardo, N. M., Dekker, F., Schmidt, M., Culmsee, C., César Cárdenas, J., Kruyt, F. & Dolga, A. M., Jan-2020, In : Biochemical Pharmacology. 171, 13 p., 113714.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Krabbendam, I. E., Honrath, B., Bothof, L., Silva-Pavez, E., Huerta, H., Peñaranda Fajardo, N. M., ... Dolga, A. M. (2020). SK channel activation potentiates auranofin-induced cell death in glio- and neuroblastoma cells. Biochemical Pharmacology, 171, [113714]. https://doi.org/10.1016/j.bcp.2019.113714

Author

Krabbendam, Inge E ; Honrath, Birgit ; Bothof, Laura ; Silva-Pavez, Eduardo ; Huerta, Hernán ; Peñaranda Fajardo, Natalia M ; Dekker, Frank ; Schmidt, Martina ; Culmsee, Carsten ; César Cárdenas, Julio ; Kruyt, Frank ; Dolga, Amalia M. / SK channel activation potentiates auranofin-induced cell death in glio- and neuroblastoma cells. In: Biochemical Pharmacology. 2020 ; Vol. 171.

Harvard

Krabbendam, IE, Honrath, B, Bothof, L, Silva-Pavez, E, Huerta, H, Peñaranda Fajardo, NM, Dekker, F, Schmidt, M, Culmsee, C, César Cárdenas, J, Kruyt, F & Dolga, AM 2020, 'SK channel activation potentiates auranofin-induced cell death in glio- and neuroblastoma cells', Biochemical Pharmacology, vol. 171, 113714. https://doi.org/10.1016/j.bcp.2019.113714

Standard

SK channel activation potentiates auranofin-induced cell death in glio- and neuroblastoma cells. / Krabbendam, Inge E; Honrath, Birgit; Bothof, Laura; Silva-Pavez, Eduardo; Huerta, Hernán; Peñaranda Fajardo, Natalia M; Dekker, Frank; Schmidt, Martina; Culmsee, Carsten; César Cárdenas, Julio; Kruyt, Frank; Dolga, Amalia M.

In: Biochemical Pharmacology, Vol. 171, 113714, 01.2020.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Krabbendam IE, Honrath B, Bothof L, Silva-Pavez E, Huerta H, Peñaranda Fajardo NM et al. SK channel activation potentiates auranofin-induced cell death in glio- and neuroblastoma cells. Biochemical Pharmacology. 2020 Jan;171. 113714. https://doi.org/10.1016/j.bcp.2019.113714


BibTeX

@article{9fd3a134ad41411f8fb55d61e4311aeb,
title = "SK channel activation potentiates auranofin-induced cell death in glio- and neuroblastoma cells",
abstract = "Brain tumours are among the deadliest tumours being highly resistant to currently available therapies. The proliferative behaviour of gliomas is strongly influenced by ion channel activity. Small-conductance calcium-activated potassium (SK/KCa) channels are a family of ion channels that are associated with cell proliferation and cell survival. A combined treatment of classical anti-cancer agents and pharmacological SK channel modulators has not been addressed yet. We used the gold-derivative auranofin to induce cancer cell death by targeting thioredoxin reductases in combination with CyPPA to activate SK channels in neuro- and glioblastoma cells. Combined treatment with auranofin and CyPPA induced massive mitochondrial damage and potentiated auranofin-induced toxicity in neuroblastoma cells in vitro. In particular, mitochondrial integrity, respiration and associated energy generation were impaired. These findings were recapitulated in patient-derived glioblastoma neurospheres yet not observed in non-cancerous HT22 cells. Taken together, integrating auranofin and SK channel openers to affect mitochondrial health was identified as a promising strategy to increase the effectiveness of anti-cancer agents and potentially overcome resistance.",
author = "Krabbendam, {Inge E} and Birgit Honrath and Laura Bothof and Eduardo Silva-Pavez and Hern{\'a}n Huerta and {Pe{\~n}aranda Fajardo}, {Natalia M} and Frank Dekker and Martina Schmidt and Carsten Culmsee and {C{\'e}sar C{\'a}rdenas}, Julio and Frank Kruyt and Dolga, {Amalia M}",
note = "Copyright {\circledC} 2019. Published by Elsevier Inc.",
year = "2020",
month = "1",
doi = "10.1016/j.bcp.2019.113714",
language = "English",
volume = "171",
journal = "Biochemical Pharmacology",
issn = "0006-2952",
publisher = "PERGAMON-ELSEVIER SCIENCE LTD",

}

RIS

TY - JOUR

T1 - SK channel activation potentiates auranofin-induced cell death in glio- and neuroblastoma cells

AU - Krabbendam, Inge E

AU - Honrath, Birgit

AU - Bothof, Laura

AU - Silva-Pavez, Eduardo

AU - Huerta, Hernán

AU - Peñaranda Fajardo, Natalia M

AU - Dekker, Frank

AU - Schmidt, Martina

AU - Culmsee, Carsten

AU - César Cárdenas, Julio

AU - Kruyt, Frank

AU - Dolga, Amalia M

N1 - Copyright © 2019. Published by Elsevier Inc.

PY - 2020/1

Y1 - 2020/1

N2 - Brain tumours are among the deadliest tumours being highly resistant to currently available therapies. The proliferative behaviour of gliomas is strongly influenced by ion channel activity. Small-conductance calcium-activated potassium (SK/KCa) channels are a family of ion channels that are associated with cell proliferation and cell survival. A combined treatment of classical anti-cancer agents and pharmacological SK channel modulators has not been addressed yet. We used the gold-derivative auranofin to induce cancer cell death by targeting thioredoxin reductases in combination with CyPPA to activate SK channels in neuro- and glioblastoma cells. Combined treatment with auranofin and CyPPA induced massive mitochondrial damage and potentiated auranofin-induced toxicity in neuroblastoma cells in vitro. In particular, mitochondrial integrity, respiration and associated energy generation were impaired. These findings were recapitulated in patient-derived glioblastoma neurospheres yet not observed in non-cancerous HT22 cells. Taken together, integrating auranofin and SK channel openers to affect mitochondrial health was identified as a promising strategy to increase the effectiveness of anti-cancer agents and potentially overcome resistance.

AB - Brain tumours are among the deadliest tumours being highly resistant to currently available therapies. The proliferative behaviour of gliomas is strongly influenced by ion channel activity. Small-conductance calcium-activated potassium (SK/KCa) channels are a family of ion channels that are associated with cell proliferation and cell survival. A combined treatment of classical anti-cancer agents and pharmacological SK channel modulators has not been addressed yet. We used the gold-derivative auranofin to induce cancer cell death by targeting thioredoxin reductases in combination with CyPPA to activate SK channels in neuro- and glioblastoma cells. Combined treatment with auranofin and CyPPA induced massive mitochondrial damage and potentiated auranofin-induced toxicity in neuroblastoma cells in vitro. In particular, mitochondrial integrity, respiration and associated energy generation were impaired. These findings were recapitulated in patient-derived glioblastoma neurospheres yet not observed in non-cancerous HT22 cells. Taken together, integrating auranofin and SK channel openers to affect mitochondrial health was identified as a promising strategy to increase the effectiveness of anti-cancer agents and potentially overcome resistance.

U2 - 10.1016/j.bcp.2019.113714

DO - 10.1016/j.bcp.2019.113714

M3 - Article

VL - 171

JO - Biochemical Pharmacology

JF - Biochemical Pharmacology

SN - 0006-2952

M1 - 113714

ER -

ID: 103411385