Transformed Root Extract of Leonurus sibiricus Induces Apoptosis through Intrinsic and Extrinsic Pathways in Various Grades of Human Glioma Cells

Pathol Oncol Res. 2017 Jul;23(3):679-687. doi: 10.1007/s12253-016-0170-6. Epub 2016 Dec 28.

Abstract

This study determines the influence of transformed root (TR) extract of Leonurus sibiricus L. on various grades (I-III) of human glioma cells derived from patients. This plant occurs in southern Asia and Siberia and is widely used as a medicinal plant with various biological activities. Chromatographic profile of TR extract have revealed the presence of various polyphenolic compounds (4-hydroxybenzoic acid, gentisic acid, vanilic acid, 1,3-dicaffeoylquinic acid, α-resorcylic acid). We found TR root extract to have antiproliferative activity on glioma cells after 24 h of treatment. TR root extract induces apoptosis on various grades (I-III) of human glioma cells by the generation of reactive oxygen species (ROS) along with concurrent loss of mitochondrial membrane potential, enhanced S and G2/M phases of the cell cycle, and altered mRNA levels of Bax, Bcl-2, p53, Cas-3, Cas-8 and Cas-9 factors involved in apoptosis. This work for the first time demonstrate that TR extract from L. sibiricus root has the potential to activate apoptosis in grade I-III human glioma cells through the intrinsic and extrinsic pathways.

Keywords: Apoptosis; Cell cycle; Gene expression; Mitochondrial membrane potential; Reactive oxygen species; Transformed roots of Leonurus sibiricus.

MeSH terms

  • Apoptosis / drug effects*
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Glioma / drug therapy*
  • Glioma / metabolism
  • Humans
  • Hydroxybenzoates / pharmacology
  • Leonurus / chemistry*
  • Membrane Potential, Mitochondrial / drug effects
  • Parabens / pharmacology
  • Plant Extracts / pharmacology*
  • Plant Roots / chemistry*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Quinic Acid / analogs & derivatives
  • Quinic Acid / pharmacology
  • Reactive Oxygen Species / metabolism
  • Resorcinols / pharmacology
  • bcl-2-Associated X Protein / metabolism

Substances

  • 1,3-dicaffeoylquinic acid
  • Hydroxybenzoates
  • Parabens
  • Plant Extracts
  • Proto-Oncogene Proteins c-bcl-2
  • Reactive Oxygen Species
  • Resorcinols
  • bcl-2-Associated X Protein
  • Quinic Acid
  • alpha-resorcylic acid
  • 4-hydroxybenzoic acid