Tumoricidal effects of unprimed and curcumin-primed adipose-derived stem cells on human hepatoma HepG2 cells under oxidative conditions

Tissue Cell. 2022 Dec:79:101968. doi: 10.1016/j.tice.2022.101968. Epub 2022 Oct 31.

Abstract

Introduction: Adipose-derived stem cells (ASCs) have been proven to have tumoricidal effects against hepatic cancer cell lines. However, it appears that exposure to oxidative microenvironment compromises the potential outcome of ASCs in real hepatoma. Herein, we aimed to examine the tumoricidal effects of ASCs under oxidative conditions and to investigate the impact of curcumin priming on ASCs' therapeutic potential.

Methods: We used human hepatoma (HepG2) cells in a coculture system with unprimed or curcumin-primed ASCs (Cur-ASCs) under H2O2-induced oxidative conditions. To investigate HepG2 proliferation and death, MTT (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) and annexin V staining assays were performed. To determine the HepG2 migration and invasion potential, the scratch healing and the transwell invasion assays were performed. To evaluate the expression of apoptosis-protein markers, Western blotting was performed.

Results: Cur-ASCs suppressed HepG2 proliferation, migration, and invasion as well as prompted apoptosis more significantly compared to unprimed ASCs under oxidative conditions. Expressional studies also revealed an obvious decline in the BCL-2/BAX ratio in HepG2 cocultured with Cur-ASCs. In addition, we noticed a marked elevation of apoptosis and senescence in unprimed ASCs compared to Cur-ASCs after coculture experiments, which demonstrated that curcumin priming preserved the survival and growth potential of ASCs; hence, Cur-ASCs performed better tumoricidal functions under oxidative conditions.

Conclusion: Our findings suggest that ASCs have the intrinsic ability to induce cell death in HepG2 cells; however, their functions can be compromised under oxidative conditions. We believe that curcumin priming is an effective approach for improving the therapeutic effectiveness of ASCs in the cancerous microenvironment.

Keywords: Adipose-derived stem cells; Curcumin; Hepatoma HepG2 cells; Oxidative stress; Priming.

MeSH terms

  • Carcinoma, Hepatocellular* / drug therapy
  • Curcumin* / pharmacology
  • Hep G2 Cells
  • Humans
  • Hydrogen Peroxide
  • Liver Neoplasms* / drug therapy
  • Oxidative Stress
  • Stem Cells
  • Tumor Microenvironment

Substances

  • Curcumin
  • Hydrogen Peroxide