Ursolic Acid-Induced Apoptosis via Regulation of the PI3K/Akt and MAPK Signaling Pathways in Huh-7 Cells

Molecules. 2018 Aug 13;23(8):2016. doi: 10.3390/molecules23082016.

Abstract

Ursolic acid (UA), is a kind of triterpene acid that exhibits wide biological properties. In this article, the effects of UA on apoptosis and the proliferation of human hepatoma Huh-7 cells were reported. The MTT results showed that cell viability of Huh-7 was reduced in a concentration and time-dependent effect. In addition, DAPI staining was used to detected condensation of chromatin in nucleus. Apoptotic cell population was examined using Annexin V/PI staining. The results showed that exposure to UA affected extrinsic and intrinsic pathways through, reduced expression of Bcl-2, Mcl-1, and TCTP; increased levels of the apoptotic proteins TNF-α, Fas, FADD, and Bax; and activation of cleaved caspase-3 and PARP. UA also inhibited the p-Akt and p38 MAPK signaling transduction pathways, and increased activity in the p-ERK signaling pathway. Taken together, UA inhibited the cell growth of Huh-7 cells and affected apoptosis, via regulated cellular signaling transduction.

Keywords: MAPK pathway; PARP; PI3K/Akt; apoptosis; caspase-3; huh-7; ursolic acid.

MeSH terms

  • Apoptosis / drug effects*
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Humans
  • MAP Kinase Signaling System / drug effects
  • Mitogen-Activated Protein Kinases / metabolism*
  • Molecular Structure
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Poly(ADP-ribose) Polymerases / genetics
  • Poly(ADP-ribose) Polymerases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction / drug effects*
  • Triterpenes / chemistry
  • Triterpenes / pharmacology*
  • Tumor Protein, Translationally-Controlled 1
  • Ursolic Acid

Substances

  • TPT1 protein, human
  • Triterpenes
  • Tumor Protein, Translationally-Controlled 1
  • Poly(ADP-ribose) Polymerases
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinases
  • CASP3 protein, human
  • Caspase 3