title: Transformed Root Extract of Leonurus sibiricus Induces Apoptosis through Intrinsic and Extrinsic Pathways in Various Grades of Human Glioma Cells.
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.
authors.affiliation: Department of Biology and Pharmaceutical Botany, Medical University of Lodz, Muszyńskiego Street 1, 90-151, Łódź, Poland. przemyslaw.sitarek@umed.lodz.pl.
authors.forename: Przemysław
authors.initials: P
authors.lastname: Sitarek
authors.affiliation: Department of Biology and Pharmaceutical Botany, Medical University of Lodz, Muszyńskiego Street 1, 90-151, Łódź, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Skała
authors.affiliation: Department of Molecular Genetics, University of Lodz, Łódź, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Toma
authors.affiliation: Department of Plant Physiology and Biochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Łódź, Poland.
authors.forename: Marzena
authors.initials: M
authors.lastname: Wielanek
authors.affiliation: Department of Medical Biochemistry, Medical University of Lodz, Łódź, Poland.
authors.forename: Janusz
authors.initials: J
authors.lastname: Szemraj
authors.affiliation: Department of Microbiology and Immunology, and Fels Institute for Cancer Research, School of Medicine, Temple University, Philadelphia, PA, USA.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Skorski
authors.affiliation: Department of Pneumology and Allergy, 1st Chair of Internal Medicine, Medical University of Lodz, Łódź, Poland.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Białas
authors.affiliation: Department of Genetics and Plant Molecular Biology and Biotechnology, The University of Lodz, Łódź, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Sakowicz
authors.affiliation: Department of Genetics and Plant Molecular Biology and Biotechnology, The University of Lodz, Łódź, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Kowalczyk
authors.affiliation: Department of Neurosurgery, Surgery of Spine and Peripheral Nerves, Medical University of Łódź, University Hospital WAM-CSW, Łódź, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Radek
authors.affiliation: Department of Biology and Pharmaceutical Botany, Medical University of Lodz, Muszyńskiego Street 1, 90-151, Łódź, Poland.
authors.forename: Halina
authors.initials: H
authors.lastname: Wysokińska
authors.affiliation: Department of Molecular Genetics, University of Lodz, Łódź, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Śliwiński
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D062385:Hydroxybenzoates / Q000494:pharmacology; D031332:Leonurus / Q000737:chemistry*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D010226:Parabens / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011801:Quinic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012118:Resorcinols / Q000494:pharmacology; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C487840:1,3-dicaffeoylquinic acid; D062385:Hydroxybenzoates; D010226:Parabens; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D012118:Resorcinols; D051028:bcl-2-Associated X Protein; D011801:Quinic Acid; C076950:alpha-resorcylic acid; C038193:4-hydroxybenzoic acid
keywords: Apoptosis; Cell cycle; Gene expression; Mitochondrial membrane potential; Reactive oxygen species; Transformed roots of Leonurus sibiricus