Macranthoidin B (MB) Promotes Oxidative Stress-Induced Inhibiting of Hepa1-6 Cell Proliferation via Selenoprotein

Biol Trace Elem Res. 2023 Jan;201(1):368-376. doi: 10.1007/s12011-022-03120-x. Epub 2022 Jan 26.

Abstract

The aim of this study was to investigate the role of selenoproteins in Macranthoidin B (MB) with regard to the inhibition of hepa1-6 cell proliferation. The CCK8 method was used to detect the inhibition rate in hepa1-6 cell of proliferation. The production of ROS, MDA, GSH levels, and GSH-Px and SOD activities was detected according to corresponding reagent kits. We determined the mRNA expressions of 25 selenoproteins in hepa1-6 cells via real-time quantitative PCR (qRT-PCR); moreover, the heat map and principal component analysis were used for further bioinformatics analysis. The results revealed that with an increasing concentration of MB, the inhibitory effect on hepa1-6 cell proliferation intensified. Compared with the control group, the treatment group showed significantly increased ROS levels, elevated MDA contents, and decreased GSH level, GSH-Px activity, and SOD activity. Increasing MB concentration treatment induced remarkable degradation of Txnrd1, Txnrd2, Txnrd3, Gpx1, Gpx2, Gpx3, Gpx6, Dio1, Dio2, Selt, Selp, Selh, Selk, Selw, Seln, and Dio3. Principal component analysis revealed that Txnrd 3, Selk, Selo, Selw, Selt, Dio2, Txnrd1, Dio3, Gpx6, and Dio1 were highly correlated with MB. In conclusion, MB dose dependently inhibited hepa1-6 cell proliferation and induced oxidative stress. Based on bioinformatics analysis, with MB treatment, Txnrd 3, Selk, Selo, Selw, Selt, Dio2, Txnrd1, Dio3, Gpx6, and Dio1 exhibited critical role in the inhibition of hepa1-6 cells proliferation. The functions of these selenoproteins were associated with oxidative stress.

Keywords: Hepa1-6; Macranthoidin B (MB); Oxidative stress; Proliferation; Selenoprotein.

MeSH terms

  • Animals
  • Cell Proliferation
  • Mice
  • Mice, Inbred Strains
  • Oxidative Stress
  • Reactive Oxygen Species
  • Selenium* / pharmacology
  • Selenoproteins / metabolism
  • Superoxide Dismutase / metabolism

Substances

  • macranthoidin B
  • Reactive Oxygen Species
  • Selenium
  • Selenoproteins
  • Superoxide Dismutase