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Bort A, Spínola E, Rodríguez-Henche N, et al. Capsaicin exerts synergistic antitumor effect with sorafenib in hepatocellular carcinoma cells through AMPK activation. Oncotarget. 2017;8(50):87684-87698doi: 10.18632/oncotarget.21196.
Bort, A., Spínola, E., Rodríguez-Henche, N., & Díaz-Laviada, I. (2017). Capsaicin exerts synergistic antitumor effect with sorafenib in hepatocellular carcinoma cells through AMPK activation. Oncotarget, 8(50), 87684-87698. https://doi.org/10.18632/oncotarget.21196
Bort, Alicia, et al. "Capsaicin exerts synergistic antitumor effect with sorafenib in hepatocellular carcinoma cells through AMPK activation." Oncotarget vol. 8,50 (2017): 87684-87698. doi: https://doi.org/10.18632/oncotarget.21196
Bort A, Spínola E, Rodríguez-Henche N, Díaz-Laviada I. Capsaicin exerts synergistic antitumor effect with sorafenib in hepatocellular carcinoma cells through AMPK activation. Oncotarget. 2017 Sep 23;8(50):87684-87698. doi: 10.18632/oncotarget.21196. eCollection 2017 Oct 20. PMID: 29152112; PMCID: PMC5675664.
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Oncotarget. 2017 Sep 23;8(50):87684-87698. doi: 10.18632/oncotarget.21196. eCollection 2017 Oct 20.

Capsaicin exerts synergistic antitumor effect with sorafenib in hepatocellular carcinoma cells through AMPK activation.

Oncotarget

Alicia Bort, Elena Spínola, Nieves Rodríguez-Henche, Inés Díaz-Laviada

Affiliations

  1. Department of Systems Biology, School of Medicine and Heath Sciences, University of Alcala, Alcalá de Henares, E-28871, Madrid, Spain.
  2. Chemical Research Institute Andrés M. del Río (IQAR), University of Alcala, Alcalá de Henares, E-28871, Madrid, Spain.

PMID: 29152112 PMCID: PMC5675664 DOI: 10.18632/oncotarget.21196

Abstract

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.

Keywords: AMPK; Akt; capsaicin; hepatocellular carcinoma; sorafenib

Conflict of interest statement

CONFLICTS OF INTEREST The authors declare no potential conflicts of interest.

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