Cancer Stem Cells of Hepatocellular Carcinoma Are Suppressed by the Voltage-gated Calcium Channel Inhibitor Amlodipine.
Anticancer Res
; 43(11): 4855-4864, 2023 Nov.
Article
en En
| MEDLINE
| ID: mdl-37909988
ABSTRACT
BACKGROUND/AIM:
The membrane transporters activated in cancer stem cells (CSCs) are the target of novel cancer therapies for hepatocellular carcinoma (HCC). The present investigation demonstrated the expression profiles of ion channels in CSCs of HCC. MATERIALS ANDMETHODS:
Cells that highly expressed aldehyde dehydrogenase 1 family member A1 (ALDH1A1) were separated from HepG2 cells, a human HCC cell line, by fluorescence-activated cell sorting, and CSCs were identified based on the formation of tumorspheres. Gene expression profiles in CSCs were investigated using microarray analysis.RESULTS:
Among HepG2 cells, ALDH1A1 messenger RNA level was higher in CSCs than in non-CSCs. Furthermore, CSCs exhibited resistance to cisplatin and had the capacity to redifferentiate. The results of the microarray analysis of CSCs showed the up-regulated expression of several genes related to ion channels, such as calcium voltage-gated channel auxiliary subunit gamma 4 (CACNG4). The cytotoxicity of the CACNG4 inhibitor amlodipine was higher at lower concentrations in CSCs than in non-CSCs, and markedly decreased the number of tumorspheres. The cell population among HepG2 cells that highly expressed ALDH1A1 was also significantly reduced by this inhibitor.CONCLUSION:
CACNG4 plays a role in maintaining CSCs, and its inhibitor, amlodipine, could potentially be a targeted therapeutic agent against HCC.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Carcinoma Hepatocelular
/
Neoplasias Hepáticas
Límite:
Humans
Idioma:
En
Revista:
Anticancer Res
Año:
2023
Tipo del documento:
Article
País de afiliación:
Japón