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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.

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Tumor Biology

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.

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Authors and Affiliations

  1. Department of Biology and Pharmaceutical Botany, Medical University of Łódź, Muszyńskiego 1, 90-151, Łódź, Poland

    Przemysław Sitarek, Ewa Skała & Halina Wysokińska

  2. Department of Molecular Genetics, University of Łódź, Pomorska 141/143, 90-236, Łódź, Poland

    Monika Toma & Tomasz Śliwiński

  3. Department of Plant Physiology and Biochemistry, Faculty of Biology and Environmental Protection, University of Łódź, Banacha 12/16, 90-237, Łódź, Poland

    Marzena Wielanek

  4. Department of Medical Biochemistry, Medical University of Łódź, Mazowiecka 6/8, 92-215, Łódź, Poland

    Janusz Szemraj

  5. Department of Microbiology and Immunology, and Fels Institute for Cancer Research, Temple University, School of Medicine, Philadelphia, PA, USA

    Malgorzata Nieborowska-Skorska & Tomasz Skorski

  6. Department of Neurosurgery, Medical University, Copernicus Memorial Hospital, Łódź, Poland

    Maciej Kolasa

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  1. Przemysław Sitarek
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Sitarek, P., Skała, E., Toma, M. et al. 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.. Tumor Biol. 37, 8753–8764 (2016). https://doi.org/10.1007/s13277-015-4714-2

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  • DOI: https://doi.org/10.1007/s13277-015-4714-2

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