Tumor Biology

, Volume 36, Issue 8, pp 6149–6158 | Cite as

Astemizole-based anticancer therapy for hepatocellular carcinoma (HCC), and Eag1 channels as potential early-stage markers of HCC

  • María de Guadalupe Chávez-López
  • Julio Isael Pérez-Carreón
  • Violeta Zuñiga-García
  • José Díaz-Chávez
  • Luis A. Herrera
  • Claudia Haydee Caro-Sánchez
  • Isabel Acuña-Macías
  • Patricio Gariglio
  • Elizabeth Hernández-Gallegos
  • Andrea Jazmín Chiliquinga
  • Javier Camacho
Research Article


Hepatocellular carcinoma (HCC) has very poor prognosis. Astemizole has gained great interest as a potential anticancer drug because it targets several proteins involved in cancer including the Eag1 (ether à-go-go-1) potassium channel that is overexpressed in human HCC. Eag1 channels are regulated by cancer etiological factors and have been proposed as early tumor markers. Here, we found that HepG2 and HuH-7 HCC cells displayed Eag1 messenger RNA (mRNA) and protein expression, determined by real-time RT-PCR and immunochemistry, respectively. Astemizole inhibited human HCC cell proliferation (assessed by metabolic activity assay) and induced apoptosis (studied with flow cytometry) in both cell lines. The subcellular Eag1 protein localization was modified by astemizole in the HepG2 cells. The treatment with astemizole prevented diethylnitrosamine (DEN)-induced rat HCC development in vivo (followed by studying γ-glutamyl transpeptidase (GGT) activity). The Eag1 mRNA and protein levels were increased in most DEN-treated groups but decreased after astemizole treatment. GGT activity was decreased by astemizole. The Eag1 protein was detected in cirrhotic and dysplastic rat livers. Astemizole might have clinical utility for HCC prevention and treatment, and Eag1 channels may be potential early HCC biomarkers. These data provide significant basis to include astemizole in HCC clinical trials.


Liver cancer Liver cirrhosis Astemizole Eag1 Tumor markers Potassium channels 



We thank Beatriz Alcántara for her secretarial work and Guadalupe Montiel and Eduardo García Osornio for their technical assistance. This work was partially supported by the Consejo Nacional de Ciencia y Tecnología (Conacyt) grant number 168102 to JC.

Compliance with Ethical Standards

Conflicts of interest


Ethical approval

This article does not contain any studies with human participants performed by any of the authors. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.


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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • María de Guadalupe Chávez-López
    • 1
  • Julio Isael Pérez-Carreón
    • 3
  • Violeta Zuñiga-García
    • 1
  • José Díaz-Chávez
    • 4
  • Luis A. Herrera
    • 4
  • Claudia Haydee Caro-Sánchez
    • 5
  • Isabel Acuña-Macías
    • 1
  • Patricio Gariglio
    • 2
  • Elizabeth Hernández-Gallegos
    • 1
  • Andrea Jazmín Chiliquinga
    • 1
  • Javier Camacho
    • 1
  1. 1.Department of PharmacologyCentro de Investigación y de Estudios Avanzados del I.P.N.Mexico CityMexico
  2. 2.Departamento de Genética y Biología MolecularCentro de Investigación y de Estudios Avanzados del I.P.N.Mexico CityMexico
  3. 3.Instituto Nacional de Medicina GenómicaMexico CityMexico
  4. 4.Unidad de Investigación Biomédica en CáncerUNAM/Instituto Nacional de CancerologíaMexico CityMexico
  5. 5.Departamento de Anatomía Patológica, Instituto de Investigaciones BiomédicasUNAM/Instituto Nacional de CancerologíaMexico CityMexico

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