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Efficacy of HDAC Inhibitors Belinostat and Panobinostat against Cisplatin-Sensitive and Cisplatin-Resistant Testicular Germ Cell Tumors

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Efficacy of HDAC Inhibitors Belinostat and Panobinostat against Cisplatin-Sensitive and Cisplatin-Resistant Testicular Germ Cell Tumors. / Lobo, João; Guimarães-Teixeira, Catarina; Barros-Silva, Daniela; Miranda-Gonçalves, Vera; Camilo, Vânia; Guimarães, Rita; Cantante, Mariana; Braga, Isaac; Maurício, Joaquina; Oing, Christoph; Honecker, Friedemann; Nettersheim, Daniel; Looijenga, Leendert Hj; Henrique, Rui; Jerónimo, Carmen.

In: CANCERS, Vol. 12, No. 10, 10.10.2020.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Lobo, J, Guimarães-Teixeira, C, Barros-Silva, D, Miranda-Gonçalves, V, Camilo, V, Guimarães, R, Cantante, M, Braga, I, Maurício, J, Oing, C, Honecker, F, Nettersheim, D, Looijenga, LH, Henrique, R & Jerónimo, C 2020, 'Efficacy of HDAC Inhibitors Belinostat and Panobinostat against Cisplatin-Sensitive and Cisplatin-Resistant Testicular Germ Cell Tumors', CANCERS, vol. 12, no. 10. https://doi.org/10.3390/cancers12102903

APA

Lobo, J., Guimarães-Teixeira, C., Barros-Silva, D., Miranda-Gonçalves, V., Camilo, V., Guimarães, R., Cantante, M., Braga, I., Maurício, J., Oing, C., Honecker, F., Nettersheim, D., Looijenga, L. H., Henrique, R., & Jerónimo, C. (2020). Efficacy of HDAC Inhibitors Belinostat and Panobinostat against Cisplatin-Sensitive and Cisplatin-Resistant Testicular Germ Cell Tumors. CANCERS, 12(10). https://doi.org/10.3390/cancers12102903

Vancouver

Lobo J, Guimarães-Teixeira C, Barros-Silva D, Miranda-Gonçalves V, Camilo V, Guimarães R et al. Efficacy of HDAC Inhibitors Belinostat and Panobinostat against Cisplatin-Sensitive and Cisplatin-Resistant Testicular Germ Cell Tumors. CANCERS. 2020 Oct 10;12(10). https://doi.org/10.3390/cancers12102903

Bibtex

@article{782f4554662847cba58ec374ac5e70ce,
title = "Efficacy of HDAC Inhibitors Belinostat and Panobinostat against Cisplatin-Sensitive and Cisplatin-Resistant Testicular Germ Cell Tumors",
abstract = "Novel treatment options are needed for testicular germ cell tumor (TGCT) patients, particularly important for those showing or developing cisplatin resistance, the major cause of cancer-related deaths. As TGCTs pathobiology is highly related to epigenetic (de)regulation, epidrugs are potentially effective therapies. Hence, we sought to explore, for the first time, the effect of the two most recently FDA-approved HDAC inhibitors (HDACis), belinostat and panobinostat, in (T)GCT cell lines including those resistant to cisplatin. In silico results were validated in 261 patient samples and differential expression of HDACs was also observed across cell lines. Belinostat and panobinostat reduced cell viability in both cisplatin-sensitive cells (NCCIT-P, 2102Ep-P, and NT2-P) and, importantly, also in matched cisplatin-resistant subclones (NCCIT-R, 2102Ep-R, and NT2-R), with IC50s in the low nanomolar range for all cell lines. Treatment of NCCIT-R with both drugs increased acetylation, induced cell cycle arrest, reduced proliferation, decreased Ki67 index, and increased p21, while increasing cell death by apoptosis, with upregulation of cleaved caspase 3. These findings support the effectiveness of HDACis for treating TGCT patients in general, including those developing cisplatin resistance. Future studies should explore them as single or combination agents.",
author = "Jo{\~a}o Lobo and Catarina Guimar{\~a}es-Teixeira and Daniela Barros-Silva and Vera Miranda-Gon{\c c}alves and V{\^a}nia Camilo and Rita Guimar{\~a}es and Mariana Cantante and Isaac Braga and Joaquina Maur{\'i}cio and Christoph Oing and Friedemann Honecker and Daniel Nettersheim and Looijenga, {Leendert Hj} and Rui Henrique and Carmen Jer{\'o}nimo",
year = "2020",
month = oct,
day = "10",
doi = "10.3390/cancers12102903",
language = "English",
volume = "12",
journal = "CANCERS",
issn = "2072-6694",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "10",

}

RIS

TY - JOUR

T1 - Efficacy of HDAC Inhibitors Belinostat and Panobinostat against Cisplatin-Sensitive and Cisplatin-Resistant Testicular Germ Cell Tumors

AU - Lobo, João

AU - Guimarães-Teixeira, Catarina

AU - Barros-Silva, Daniela

AU - Miranda-Gonçalves, Vera

AU - Camilo, Vânia

AU - Guimarães, Rita

AU - Cantante, Mariana

AU - Braga, Isaac

AU - Maurício, Joaquina

AU - Oing, Christoph

AU - Honecker, Friedemann

AU - Nettersheim, Daniel

AU - Looijenga, Leendert Hj

AU - Henrique, Rui

AU - Jerónimo, Carmen

PY - 2020/10/10

Y1 - 2020/10/10

N2 - Novel treatment options are needed for testicular germ cell tumor (TGCT) patients, particularly important for those showing or developing cisplatin resistance, the major cause of cancer-related deaths. As TGCTs pathobiology is highly related to epigenetic (de)regulation, epidrugs are potentially effective therapies. Hence, we sought to explore, for the first time, the effect of the two most recently FDA-approved HDAC inhibitors (HDACis), belinostat and panobinostat, in (T)GCT cell lines including those resistant to cisplatin. In silico results were validated in 261 patient samples and differential expression of HDACs was also observed across cell lines. Belinostat and panobinostat reduced cell viability in both cisplatin-sensitive cells (NCCIT-P, 2102Ep-P, and NT2-P) and, importantly, also in matched cisplatin-resistant subclones (NCCIT-R, 2102Ep-R, and NT2-R), with IC50s in the low nanomolar range for all cell lines. Treatment of NCCIT-R with both drugs increased acetylation, induced cell cycle arrest, reduced proliferation, decreased Ki67 index, and increased p21, while increasing cell death by apoptosis, with upregulation of cleaved caspase 3. These findings support the effectiveness of HDACis for treating TGCT patients in general, including those developing cisplatin resistance. Future studies should explore them as single or combination agents.

AB - Novel treatment options are needed for testicular germ cell tumor (TGCT) patients, particularly important for those showing or developing cisplatin resistance, the major cause of cancer-related deaths. As TGCTs pathobiology is highly related to epigenetic (de)regulation, epidrugs are potentially effective therapies. Hence, we sought to explore, for the first time, the effect of the two most recently FDA-approved HDAC inhibitors (HDACis), belinostat and panobinostat, in (T)GCT cell lines including those resistant to cisplatin. In silico results were validated in 261 patient samples and differential expression of HDACs was also observed across cell lines. Belinostat and panobinostat reduced cell viability in both cisplatin-sensitive cells (NCCIT-P, 2102Ep-P, and NT2-P) and, importantly, also in matched cisplatin-resistant subclones (NCCIT-R, 2102Ep-R, and NT2-R), with IC50s in the low nanomolar range for all cell lines. Treatment of NCCIT-R with both drugs increased acetylation, induced cell cycle arrest, reduced proliferation, decreased Ki67 index, and increased p21, while increasing cell death by apoptosis, with upregulation of cleaved caspase 3. These findings support the effectiveness of HDACis for treating TGCT patients in general, including those developing cisplatin resistance. Future studies should explore them as single or combination agents.

U2 - 10.3390/cancers12102903

DO - 10.3390/cancers12102903

M3 - SCORING: Journal article

C2 - 33050470

VL - 12

JO - CANCERS

JF - CANCERS

SN - 2072-6694

IS - 10

ER -