ENHANCED p53-DEPENDENT GROWTH INHIBITION OF HUMAN GLIOBLASTOMA CELLS BY COMBINATORIAL TREATMENT OF TEMOZOLOMIDE AND NOVEL PURIFIED NATURAL CARBOHYDRATE OF PLEUROTUS FLORIDA

Objective: This study was designed to analyze the combinatorial chemotherapeutic effect of temozolomide (TMZ), the most common drug in glioblastoma treatment and a purified carbohydrate (Fr-II) from the edible mushroom Pleurotus florida, on human glioblastoma cell lines.Methods: Fr-II was purified by size-exclusion chromatography and characterised by different mass spectroscopy analysis. Human glioblastoma cells were treated with TMZ, Fr-II, and combination of TMZ and Fr-II. Cell cytotoxicity was measured by MTT assay, cell cycle phase distribution was determined by cell cycle analysis and followed by the relative p53 protein expression was analyzed by western blot analysis.Results: Chemical analysis of Fr-II confirmed the glycosidically linked two units of glucose with terminally attached mannitol with mass of 506 Da. Fr-II treatment exhibited cytotoxicity in both the cell lines in a dose-dependent manner with most effective dose at 200µg/ml. When Fr-II (200µg/ml) was combined with a dose range of TMZ it showed a more cellular cytotoxicity compared to the cytotoxicity of TMZ alone with most oppressive combinatorial dose at 400µM (TMZ)+200µg/ml (Fr-II). In compliance, with the above results, both cell lines showed a 10% increase in no. of cells (p<0.05) in G2/M phase indicating an arrest of cell cycle and increased p53 protein expression (p<0.05) at the combinatorial dose than TMZ alone at 400µM, but Fr-II alone didn’t show any cell cycle arrest nor did it show increased p53 expression.Conclusion: Therefore it confirms that Fr-II synergizes with TMZ to significantly intensify its anti-proliferative properties, thereby emerging as an effective element for combinatorial treatment of glioblastoma.

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Effect of the specific P53 stabilizer CBS9106 on multiple myeloma (MM)

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.8601 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 8601-8601

Author(s):

H. Ikeda ◽

T. Hideshima ◽

G. Perrone ◽

Y. Okawa ◽

N. Raje ◽

...

Keyword(s):

Cell Cycle ◽

Multiple Myeloma ◽

Protein Expression ◽

Tumor Cells ◽

Cell Lines ◽

Primary Tumor ◽

P53 Protein ◽

Wild Type ◽

Cycle Arrest ◽

P53 Protein Expression

8601 Background: The mutations of P53 tumor suppressor protein are associated with progressive in Multiple Myeloma (MM), conversely, stabilization of P53 leads to cell cycle arrest and apoptosis. In this study, we examined p53 protein expression and demonstrated the effect of P53 stabilization using a novel specific P53 stabilizer CBS9106 in MM. Method: We examined P53 protein expression using Immunoblot analysis, as well as the growth inhibitory effect of CBS9106 in MM cell lines and primary tumor cells from MM patients. We also defined whether CBS9106 can overcome the growth promoting effect of exogenous cytokines and bone marrow stroma cells (BMSCs) using [3H]-thymidine uptake assay. Results: Expression of P53 protein was observed in 3/3 primary tumor cells from MM patients and 6/6 MM cell lines. CBS9106 at low nM levels triggered cytotoxicity against p53 wild type MM cell lines and primary tumor cells from MM patients, associated with phosphorylation of P53 (serine15 and 20). In contrast, CBS9106 did not affect the survival of normal peripheral blood mononuclear cells from healthy volunteers at concentrations as high as 10 μM. This agent also induced G1 cell cycle arrest, followed by apoptosis associated with cleavage of caspase-3, -8, -9 and PARP. Neither growth stimulating cytokines (IL-6 and IGF-1) nor BMSCs protected against apoptotic effect of CBS9106. Moreover, we demonstrate that combination of CBS9106 with MDM2 inhibitor Nutrin3 or proteasome inhibitor bortezomib induces synergistic anti-MM activity in both P53 wild type MM cell lines and primary tumor cells from MM patients. Conclusions: Stabilizing P53 by CBS9106 represents a novel promising p53-based therapy in MM. These results provide the preclinical framework supporting evaluation of CBS9106 in clinical trials to improve patient outcome in MM. No significant financial relationships to disclose.

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Effects of low energy protons on clonogenic survival, DSB repair and cell cycle in human glioblastoma cells and B14 fibroblasts

Radiotherapy and Oncology ◽

10.1016/s0167-8140(04)80030-6 ◽

2004 ◽

Vol 73 ◽

pp. S115-S118 ◽

Cited By ~ 14

Author(s):

Heinrich Moertel ◽

Jens-Christoph Georgi ◽

Luitpold Distel ◽

Wolfgang Eyrich ◽

Miriam Fritsch ◽

...

Keyword(s):

Cell Cycle ◽

Clonogenic Survival ◽

Low Energy ◽

Glioblastoma Cells ◽

Dsb Repair ◽

Human Glioblastoma ◽

Human Glioblastoma Cells

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Diazepam Inhibits Proliferation of Human Glioblastoma Cells Through Triggering a G0/G1 Cell Cycle Arrest

Journal of Neurosurgical Anesthesiology ◽

10.1097/ana.0b013e31828bac6a ◽

2013 ◽

Vol 25 (3) ◽

pp. 285-291 ◽

Cited By ~ 6

Author(s):

Jingkao Chen ◽

Ying Ouyang ◽

Lin Cao ◽

Wenbo Zhu ◽

Yuxi Zhou ◽

...

Keyword(s):

Cell Cycle ◽

Cell Cycle Arrest ◽

Glioblastoma Cells ◽

Human Glioblastoma ◽

Cycle Arrest ◽

G1 Cell Cycle Arrest ◽

Human Glioblastoma Cells

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Relation between intracellular location and photodynamic efficacy of 5-aminolevulinic acid-induced protoporphyrin IXin vitro. Comparison between human glioblastoma cells and other cancer cell lines

Photochemical & Photobiological Sciences ◽

10.1039/b611715e ◽

2007 ◽

Vol 6 (2) ◽

pp. 145-151 ◽

Cited By ~ 27

Author(s):

Reinhard Sailer ◽

Wolfgang S. L. Strauss ◽

Michael Wagner ◽

Helmut Emmert ◽

Herbert Schneckenburger

Keyword(s):

Cell Lines ◽

Cancer Cell ◽

Aminolevulinic Acid ◽

Cancer Cell Lines ◽

Glioblastoma Cells ◽

Intracellular Location ◽

Human Glioblastoma ◽

Human Glioblastoma Cells

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Smarcd1 Inhibits the Malignant Phenotypes of Human Glioblastoma Cells via Crosstalk with Notch1

Molecular Neurobiology ◽

10.1007/s12035-020-02190-z ◽

2020 ◽

Author(s):

Yihao Zhu ◽

Handong Wang ◽

Maoxing Fei ◽

Ting Tang ◽

Wenhao Niu ◽

...

Keyword(s):

Cell Proliferation ◽

Cell Lines ◽

High Grade Glioma ◽

Glioblastoma Cell ◽

Glioblastoma Cells ◽

Human Glioblastoma ◽

Protein Levels ◽

Enhanced Expression ◽

Human Glioblastoma Cells ◽

Glioblastoma Cell Lines

AbstractSmarcd1 is a component of an evolutionary conserved chromatin remodeling complex—SWI/SNF, which is involved in transcription factor recruitment, DNA replication, recombination, and repair. Suppression of the SWI/SNF complex required for cellular differentiation and gene regulation may be inducible for cell proliferation and tumorigenicity. However, the inhibitory role of Smarcd1 in human glioblastoma cells has not been well illustrated. Both U87 and U251 human glioblastoma cell lines were employed in the present study. The lentivirus-mediated gene knockdown and overexpression approach was conducted to determine the function of Smarcd1. The protein levels were tested by western blot, and the relative mRNA contents were detected by quantitative real-time PCR. Cell viability was tested by CCK-8 and colony-forming assay. Transwell assays were utilized to evaluate the motility and invasive ability. Flow cytometry was employed to analyze cell cycle and apoptosis. SPSS software was used for statistical analysis. Low expression of Smarcd1 was observed in glioblastoma cell lines and in patients with high-grade glioma. Importantly, the depletion of Smarcd1 promoted cell proliferation, invasion, and chemoresistance, whereas enhanced expression of Smarcd1 inhibited tumor-malignant phenotypes. Mechanistic research demonstrated that overexpression of Smarcd1 decreased the expression of Notch1, while knockdown of Notch1 increased the expression of Smarcd1 through Hes1 suppression. Hence, the crosstalk between Smarcd1 and Notch1, which formed a feedback loop, was crucial in regulation of glioblastoma malignant phenotypes. Furthermore, targeting Smarcd1 could be a potential strategy for human glioblastoma treatment.

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