title: A preliminary study of apoptosis induction in glioma cells via alteration of the Bax/Bcl-2-p53 axis by transformed and non-transformed root extracts of Leonurus sibiricus L.
abstract: Leonurus sibiricus L. is a traditional medicinal plant which occurs in southern Siberia, China, Korea, Japan, and Vietnam. The plant shows several pharmacological effects, but the most interesting is its anti-cancer activity. The aim of our study was to examine the induction of apoptosis in malignant glioma cells, the most aggressive primary brain tumors of the central nervous system, following treatment with transformed root (TR) or non-transformed root (NR) L. sibiricus extracts. Both the NR and TR extracts were found to have cytotoxic activity in the glioma primary cells. The human glioblastoma cell lines obtained from patients were confirmed to be tumorogenic by the following three markers: D10S1709, D10S1172, and D22S283. HPLC and MS analysis revealed the presence of polyphenolic compounds (chlorogenic acid, ferulic acid, caffeic acid, p-coumaric acid, ellagic acid, and verbascoside) in both sets of root extracts. In summary, our findings demonstrate that treatment of the glioma cells with NR and TR extracts resulted (a) in significant cell growth inhibition, (b) S- and G2/M-phase cell cycle arrest, and (c) apoptosis in a dose-dependent fashion by changing Bax/Bcl-2 ratio (about 4-fold increase) and p53 (5-fold increase) activation. These findings indicate that NR and TR extracts exhibit anti-cancer activity through the regulation of genes involved in apoptosis. This is the first report to demonstrate the cytotoxic effect of polyphenolic extracts from L. sibiricus roots against glioma cells, but further studies are required to understand the complete mechanism of its apoptosic activity.
authors.affiliation: Department of Biology and Pharmaceutical Botany, Medical University of Łódź, Muszyńskiego 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 Łódź, Muszyńskiego 1, 90-151, Łódź, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Skała
authors.affiliation: Department of Molecular Genetics, University of Łódź, Pomorska 141/143, 90-236, 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 Łódź, Banacha 12/16, 90-237, Łódź, Poland.
authors.forename: Marzena
authors.initials: M
authors.lastname: Wielanek
authors.affiliation: Department of Medical Biochemistry, Medical University of Łódź, Mazowiecka 6/8, 92-215, Łódź, Poland.
authors.forename: Janusz
authors.initials: J
authors.lastname: Szemraj
authors.affiliation: Department of Microbiology and Immunology, and Fels Institute for Cancer Research, Temple University, School of Medicine, Philadelphia, PA, USA.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Nieborowska-Skorska
authors.affiliation: Department of Neurosurgery, Medical University, Copernicus Memorial Hospital, Łódź, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Kolasa
authors.affiliation: Department of Microbiology and Immunology, and Fels Institute for Cancer Research, Temple University, School of Medicine, Philadelphia, PA, USA.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Skorski
authors.affiliation: Department of Biology and Pharmaceutical Botany, Medical University of Łódź, Muszyńskiego 1, 90-151, Łódź, Poland.
authors.forename: Halina
authors.initials: H
authors.lastname: Wysokińska
authors.affiliation: Department of Molecular Genetics, University of Łódź, Pomorska 141/143, 90-236, Łódź, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Śliwiński
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D014408:Biomarkers, Tumor / Q000378:metabolism; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism; D063646:Carcinogenesis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D031332:Leonurus / Q000737:chemistry*; D008875:Middle Aged; D010936:Plant Extracts / Q000494:pharmacology; D018517:Plant Roots / Q000737:chemistry*; D010946:Plants, Medicinal / Q000737:chemistry; D059808:Polyphenols / Q000737:chemistry / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D010936:Plant Extracts; D059808:Polyphenols; D019253:Proto-Oncogene Proteins c-bcl-2; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein
keywords: Apoptosis; Gene expression; Glioma cells; Leonurus sibiricus; Phenolic compounds; Transformed roots