Cancer Stem Cells of Hepatocellular Carcinoma Are Suppressed by the Voltage-gated Calcium Channel Inhibitor Amlodipine
Year: 2023
Type: article
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 AND METHODS: 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.
Source: Anticancer Research
Institution: Kyoto Prefectural University of Medicine
Language: English
Topic: Cancer Cells and Metastasis
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: The development of targeterd therapies for Intra-mitochondrial calcium ion dinamics in colorectal cancer stem cells, Development of novel therapeutics against ion transporters expressed in cancer-associated fibroblast, The development of hypoosmotic therapy targeting volume-activated anion channels for peritoneal dissemination of colorectal cancer., The development of novel targeted therapies to over-expressed ion transporters in cancer stem cells of esophagogastric junctional and esophageal adenocarcinoma., The development of cancer-stem cells-targeted hypotoic therapies under the regulation of calsium ion tranporter, Development of novel hypotonic intraperitoneal chemotherapy based on the expression level of SLCO2A1 in gastric cancer, Functional analysis of voltage-gated potassium channels in pancreatic cancer stem cells
OpenAlex ID: W4388127705