Seleno-β-lactoglobulin (Se-β-Lg) induces mitochondria-dependant apoptosis in HepG2 cells

Mol Biol Rep. 2019 Oct;46(5):5025-5031. doi: 10.1007/s11033-019-04953-x. Epub 2019 Jul 30.

Abstract

Selenium compounds have been widely investigated as novel anticancer agents due to high efficacy and selectivity against cancer cells in recent years. This study aimed to research the potential inhibitory effects of seleno-β-lactoglobulin (Se-β-Lg) on HepG2 cells in vitro. MTT results demonstrated that the synthetized Se-β-Lg exhibited strong antitumor activity on HepG2 cells with few side effects on human normal cells (LO2) and relatively weaker cytotoxic effects compared to inorganic selenium (SeO2). Scanning electron microscope (SEM), hoechst 33342/PI double staining, annexin V-FITC/PI staining and cell cycle detection results showed that Se-β-Lg could induce the apoptosis of HepG2 cells via arresting them in S and G2/M phases and lead to the obvious morphological changes (loss of adhesion, cell shrinkage, and membrane blebbing, membrane permeabilities and DNA fragmentation). Besides, JC-1 staining, western blotting (WB) and polymerase chain reaction (PCR) results showed that Se-β-Lg could gradually destroy the mitochondrial membrane potential of HepG2 cells, and finally resulting in the mitochondria-dependant apoptosis via up-regulation of Bax, Cytochrome c, Caspase-3 and down-regulation of Bcl-2. Our data could provide a theoretical basis for practical application of Se-β-Lg in food and drug industries.

Keywords: Cell apoptosis; Mitochondria pathway; Seleno-β-lactoglobulin (Se-β-Lg).

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Hep G2 Cells
  • Humans
  • Lactoglobulins / pharmacology*
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / pathology
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / metabolism
  • Organoselenium Compounds / pharmacology*
  • Signal Transduction / drug effects

Substances

  • Antineoplastic Agents
  • Lactoglobulins
  • Organoselenium Compounds