Capsaicin exerts synergistic antitumor effect with sorafenib inhepatocellular carcinoma cells through AMPK activation

In this study, we investigated the antitumoral effects of combined treatment using sorafenib and capsaicin in hepatocellular carcinoma (HCC) cells. Here we showed that the combination of the two drugs had a much stronger inhibitory effect on both HepG2 and Huh-7 human HCC cells growth than either dr...

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Autores: Bort Bueno, Alicia Carmen|||0000-0003-1490-5823, Spinola Lasso, Elena, Rodríguez Henche, María de las Nieves|||0000-0001-9798-359X, Díaz-Laviada Marturet, Inés Cecilia|||0000-0001-9704-4373
Tipo de recurso: artículo
Fecha de publicación:2017
País:España
Institución:Universidad de Alcalá (UAH)
Repositorio:e_Buah Biblioteca Digital Universidad de Alcalá
Idioma:inglés
OAI Identifier:oai:ebuah.uah.es:10017/60382
Acceso en línea:http://hdl.handle.net/10017/60382
https://dx.doi.org/10.18632/oncotarget.21196
Access Level:acceso abierto
Palabra clave:capsaicin
sorafenib
AMPK
Akt
hepatocellular carcinoma
Medicina
Medicine
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network_acronym_str ES
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repository_id_str
spelling Capsaicin exerts synergistic antitumor effect with sorafenib inhepatocellular carcinoma cells through AMPK activationBort Bueno, Alicia Carmen|||0000-0003-1490-5823Spinola Lasso, ElenaRodríguez Henche, María de las Nieves|||0000-0001-9798-359XDíaz-Laviada Marturet, Inés Cecilia|||0000-0001-9704-4373capsaicinsorafenibAMPKAkthepatocellular carcinomaMedicinaMedicineIn this study, we investigated the antitumoral effects of combined treatment using sorafenib and capsaicin in hepatocellular carcinoma (HCC) cells. Here we showed that the combination of the two drugs had a much stronger inhibitory effect on both HepG2 and Huh-7 human HCC cells growth than either drug alone. The isobolograms demonstrated that the combinations investigated in this study produced a synergistic interaction. In the combination treatment using capsaicin and sorafenib, increased apoptosis, followed by the activation of caspase-9 and PARP, was observed. In addition, the present study demonstrated that sorafenib treatment induces activation of Akt, probably as a mechanism of resistance, whereas capsaicin inhibits Akt providing a possible pathway whereby capsaicin sensitizes to sorafenib in HCC cells. Moreover, capsaicin singly and the combination of capsaicin and sorafenib induce AMPK activation and Acetyl CoA carboxylase phosphorylation in HCC cells. Knocking down of AMPK by selective siRNA abrogates capsaicin-induced Akt inhibition, suggesting the involvement of AMPK in the antiproliferative effect. In vivo experiments further showed that that the anti-tumor effect of sorafenib was enhanced by its combination with 2.5 mg/Kg of capsaicin. Overall, these results show that combined treatment with capsaicin and sorafenib might improve sorafenib sensitivity and therefore it represents a promising and attractive strategy for the treatment of HCC.20172017-09-23journal articlehttp://purl.org/coar/resource_type/c_6501NAhttp://purl.org/coar/version/c_be7fb7dd8ff6fe43info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10017/60382https://dx.doi.org/10.18632/oncotarget.21196reponame:e_Buah Biblioteca Digital Universidad de Alcaláinstname:Universidad de Alcalá (UAH)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:ebuah.uah.es:10017/603822026-06-18T11:13:07Z
dc.title.none.fl_str_mv Capsaicin exerts synergistic antitumor effect with sorafenib inhepatocellular carcinoma cells through AMPK activation
title Capsaicin exerts synergistic antitumor effect with sorafenib inhepatocellular carcinoma cells through AMPK activation
spellingShingle Capsaicin exerts synergistic antitumor effect with sorafenib inhepatocellular carcinoma cells through AMPK activation
Bort Bueno, Alicia Carmen|||0000-0003-1490-5823
capsaicin
sorafenib
AMPK
Akt
hepatocellular carcinoma
Medicina
Medicine
title_short Capsaicin exerts synergistic antitumor effect with sorafenib inhepatocellular carcinoma cells through AMPK activation
title_full Capsaicin exerts synergistic antitumor effect with sorafenib inhepatocellular carcinoma cells through AMPK activation
title_fullStr Capsaicin exerts synergistic antitumor effect with sorafenib inhepatocellular carcinoma cells through AMPK activation
title_full_unstemmed Capsaicin exerts synergistic antitumor effect with sorafenib inhepatocellular carcinoma cells through AMPK activation
title_sort Capsaicin exerts synergistic antitumor effect with sorafenib inhepatocellular carcinoma cells through AMPK activation
dc.creator.none.fl_str_mv Bort Bueno, Alicia Carmen|||0000-0003-1490-5823
Spinola Lasso, Elena
Rodríguez Henche, María de las Nieves|||0000-0001-9798-359X
Díaz-Laviada Marturet, Inés Cecilia|||0000-0001-9704-4373
author Bort Bueno, Alicia Carmen|||0000-0003-1490-5823
author_facet Bort Bueno, Alicia Carmen|||0000-0003-1490-5823
Spinola Lasso, Elena
Rodríguez Henche, María de las Nieves|||0000-0001-9798-359X
Díaz-Laviada Marturet, Inés Cecilia|||0000-0001-9704-4373
author_role author
author2 Spinola Lasso, Elena
Rodríguez Henche, María de las Nieves|||0000-0001-9798-359X
Díaz-Laviada Marturet, Inés Cecilia|||0000-0001-9704-4373
author2_role author
author
author
dc.subject.none.fl_str_mv capsaicin
sorafenib
AMPK
Akt
hepatocellular carcinoma
Medicina
Medicine
topic capsaicin
sorafenib
AMPK
Akt
hepatocellular carcinoma
Medicina
Medicine
description In this study, we investigated the antitumoral effects of combined treatment using sorafenib and capsaicin in hepatocellular carcinoma (HCC) cells. Here we showed that the combination of the two drugs had a much stronger inhibitory effect on both HepG2 and Huh-7 human HCC cells growth than either drug alone. The isobolograms demonstrated that the combinations investigated in this study produced a synergistic interaction. In the combination treatment using capsaicin and sorafenib, increased apoptosis, followed by the activation of caspase-9 and PARP, was observed. In addition, the present study demonstrated that sorafenib treatment induces activation of Akt, probably as a mechanism of resistance, whereas capsaicin inhibits Akt providing a possible pathway whereby capsaicin sensitizes to sorafenib in HCC cells. Moreover, capsaicin singly and the combination of capsaicin and sorafenib induce AMPK activation and Acetyl CoA carboxylase phosphorylation in HCC cells. Knocking down of AMPK by selective siRNA abrogates capsaicin-induced Akt inhibition, suggesting the involvement of AMPK in the antiproliferative effect. In vivo experiments further showed that that the anti-tumor effect of sorafenib was enhanced by its combination with 2.5 mg/Kg of capsaicin. Overall, these results show that combined treatment with capsaicin and sorafenib might improve sorafenib sensitivity and therefore it represents a promising and attractive strategy for the treatment of HCC.
publishDate 2017
dc.date.none.fl_str_mv 2017
2017-09-23
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
NA
http://purl.org/coar/version/c_be7fb7dd8ff6fe43
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10017/60382
https://dx.doi.org/10.18632/oncotarget.21196
url http://hdl.handle.net/10017/60382
https://dx.doi.org/10.18632/oncotarget.21196
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:e_Buah Biblioteca Digital Universidad de Alcalá
instname:Universidad de Alcalá (UAH)
instname_str Universidad de Alcalá (UAH)
reponame_str e_Buah Biblioteca Digital Universidad de Alcalá
collection e_Buah Biblioteca Digital Universidad de Alcalá
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300724

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