NDLI: Valproic Acid Induced Differentiation and Potentiated Efficacy of Taxol and Nanotaxol for Controlling Growth of Human Glioblastoma LN18 and T98G Cells

Content Provider	Springer Nature Link
Author	Roy Choudhury, Subhasree Karmakar, Surajit Banik, Naren L. Ray, Swapan K.
Copyright Year	2011
Abstract	Glioblastoma shows poor response to current therapies and warrants new therapeutic strategies. We examined the efficacy of combination of valproic acid (VPA) and taxol (TX) or nanotaxol (NTX) in human glioblastoma LN18 and T98G cell lines. Cell differentiation was manifested in changes in morphological features and biochemical markers. Cell growth was controlled with down regulation of vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), nuclear factor-kappa B (NF-κB), phospho-Akt (p-Akt), and multi-drug resistance (MDR) marker, indicating suppression of angiogenic, survival, and multi-drug resistance pathways. Cell cycle analysis showed that combination therapy (VPA and TX or NTX) increased the apoptotic sub G1 population and apoptosis was further confirmed by Annexin V-FITC/PI binding assay and scanning electron microscopy. Combination therapy caused activation of caspase-8 and cleavage of Bid to tBid and increased Bax:Bcl-2 ratio and mitochondrial release of cytochrome c and apoptosis-inducing factor (AIF). Upregulation of calpain and caspases (caspase-9 and caspase-3) and substrate degradation were also detected in course of apoptosis. The combination of VPA and NTX most effectively controlled the growth of LN18 and T98G cells. Therefore, this combination of drugs can be used as an effective treatment for controlling growth of human glioblastoma cells.
Starting Page	2292
Ending Page	2305
Page Count	14
File Format	PDF
ISSN	03643190
Journal	Neurochemical Research
Volume Number	36
Issue Number	12
e-ISSN	15736903
Language	English
Publisher	Springer US
Publisher Date	2011-07-24
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Apoptosis Glioblastoma Nanotaxol Taxol Valproic acid Neurochemistry Cell Biology Neurology Biochemistry Neurosciences
Content Type	Text
Resource Type	Article
Subject	Medicine Biochemistry Cellular and Molecular Neuroscience

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