Hepatocellular Carcinoma Cells with Downregulated ZEB2 Become Resistant to Resveratrol by Concomitant Induction of ABCG2 Expression

Balcik-Ercin P., Cetin M., Yalim-Camci I., Uygur T., Yagci T.

MOLECULAR BIOLOGY, vol.54, no.1, pp.75-81, 2020 (SCI-Expanded) identifier

  • Publication Type: Article / Article
  • Volume: 54 Issue: 1
  • Publication Date: 2020
  • Doi Number: 10.1134/s0026893320010033
  • Journal Name: MOLECULAR BIOLOGY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, EMBASE, Veterinary Science Database
  • Page Numbers: pp.75-81
  • Keywords: hepatocellular carcinoma, cancer stem cells, epithelial-to-mesenchymal transition, ZEB2, ABCG2, drug resistance, resveratrol, CANCER STEM-CELLS, DRUG-RESISTANCE, CYCLE ARREST, APOPTOSIS, POPULATION, INHIBITION, PATHWAY, EMT
  • Dokuz Eylül University Affiliated: No

Abstract

In hepatocellular carcinoma (HCC), the presence of cancer stem cells (CSCs) have been linked to drug resistance, epithelial-mesenchymal transition (EMT), and cancer relapse. This study investigates the expression profile of ZEB1, ZEB2, ABCG2 in HCC-CSCs, and the role of EMT promoter ZEB2 in cells treated with resveratrol. The expression of ZEB1, ZEB2 and ABCG2 transcripts were analyzed in CD133(+)/CD44(+) cells isolated from the PLC/PRF/5 cell line. ZEB2-dependent ABCG2 gene expression and the effects of resveratrol on proliferation, cell cycle and apoptosis were explored in SNU398 cell clones. An inverse correlation between ZEB1/ZEB2 and ABCG2 levels were observed both in CSCs and in ZEB2-knockdown cells. The resveratrol treatment significantly decreased cell viability, while promoting cell cycle arrest in ZEB2-independent manner. Interestingly, resveratrol-treated cells with low levels of ZEB2 were resistant to apoptosis. The interplay of expression levels of ABCG2 and ZEB family EMT transcription factors may play a role in establishing CSC-like phenotype in HCC cells resistant to resveratrol.