Bacoside A Induced Sub-G0 Arrest and Early Apoptosis in Human Glioblastoma Cell Line U-87 MG through Notch Signaling Pathway
Autor: | Madhuri G S Aithal, Narayanappa Rajeswari |
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Rok vydání: | 2018 |
Předmět: |
Cell cycle checkpoint
Notch Notch signaling pathway Apoptosis Cell cycle 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Medicine Bacopa monnieri HES1 Bacoside A General Environmental Science biology business.industry biology.organism_classification chemistry 030220 oncology & carcinogenesis Cancer research General Earth and Planetary Sciences Original Article Gene expression Signal transduction business Glioblastoma 030217 neurology & neurosurgery |
Zdroj: | Brain Tumor Research and Treatment |
ISSN: | 2288-2405 |
Popis: | Background Glioblastoma multiforme (GBM) is a highly malignant brain tumor with a worst prognosis of less than one year despite advance treatment facilities. Among various signaling pathway genes displaying genetic modifications, aberrant expression of Notch pathway genes is frequent in GBM offering novel therapeutic targets. Herbal extracts having anticancer properties are used in adjuvant therapy that is safe and affordable as compared to chemotherapeutics. Bacopa monnieri has been used for the development of brain cells because of its neuroprotective properties. Its anticancer properties have shown to be promising in cancer treatment. Methods The anticancer properties of Bacoside A, an active and abundant component of Bacopa monnieri was assessed on U-87 MG cell line and its effects on expression of Notch pathway genes were studied. Cell cycle arrest and apoptosis were studied using flow cytometry. Expression of Notch pathway genes comprising of Notch receptors (notch1, notch2, notch3 and notch4), ligands (jagged1 and jagged2), a component of gamma-secretase complex (APH1A) and downstream target (HES1) were evaluated by quantitative real-time PCR. Results Bacoside A exhibited considerable cytotoxicity on U-87 MG cells inducing cell cycle arrest and apoptosis. Cell cycle analysis revealed a significant arrest of 39.21% cells in sub-G0 phase at 80 μg/mL concentration, increasing to 53.21% at a higher concentration of 100 μg/mL. The fraction of early apoptotic cells in control was low (3.48%) that increased substantially to 31.36% and 41.11% after 80 μg/mL and 100 μg/mL of Bacoside A treatment respectively. Additionally, the expression of notch1 gene decreased after exposure to Bacoside A with a fold change of 0.05, whereas HES1 gene expression was increased by 25 fold. Conclusion These data indicate that Bacoside A has a possible anticancer activity that could be inducing cell cycle arrest and apoptosis through Notch pathway in GBM in vitro. |
Databáze: | OpenAIRE |
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