Profiling of Aldehyde Dehydrogenase Isoforms in In Vitro Formed Tumorspheres

Anticancer Res. 2021 Nov;41(11):5481-5488. doi: 10.21873/anticanres.15361.

Abstract

Background/aim: Aldehyde dehydrogenases (ALDHs) are considered as markers for normal and cancer stem cells (CSC) and are involved in cell metabolism, proliferation, differentiation, stemness, and retinoic acid (RA) biosynthesis. The aim of the present study was to identify the ALDH isoforms that are associated with the CSC phenotype in non-small cell lung and hepatocellular carcinomas.

Materials and methods: We utilized lung (A549) and hepatocellular (HepG2) cancer cells and generated tumor spheres to isolate the CSC sub-population.

Results: The CSC enrichment was confirmed by the up-regulation of various CSC-related genes. Comparative qPCR analysis indicated the up-regulation of several ALDH isoforms in A549 and HepG2 spheres. Interestingly, cyclin D1 and Akt, down-stream targets of the RA signaling pathway, were also shown to be significantly up-regulated in both sphere populations.

Conclusion: Specific ALDH isoforms appear to be important mediators for the acquisition of an CSC phenotype and thus, are potential promising targets for CSC-based therapeutic approaches in lung and hepatocellular carcinomas.

Keywords: A549; ALDH; ALDH3A1; CSC markers; HepG2; cancer stem cells (CSCs).

MeSH terms

  • A549 Cells
  • Aldehyde Dehydrogenase / genetics
  • Aldehyde Dehydrogenase / metabolism*
  • Carcinoma, Hepatocellular / enzymology*
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / pathology
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Hep G2 Cells
  • Humans
  • Isoenzymes
  • Liver Neoplasms / enzymology*
  • Liver Neoplasms / genetics
  • Liver Neoplasms / pathology
  • Lung Neoplasms / enzymology*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Neoplastic Stem Cells / enzymology*
  • Neoplastic Stem Cells / pathology
  • Phenotype
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction
  • Spheroids, Cellular

Substances

  • CCND1 protein, human
  • Isoenzymes
  • Cyclin D1
  • Aldehyde Dehydrogenase
  • Proto-Oncogene Proteins c-akt