Synergistic efficacy of sorafenib and genistein in growth inhibition by down regulating angiogenic and survival factors and increasing apoptosis through upregulation of p53 and p21 in malignant neuroblastoma cells having N-Myc amplification or non-amplification

Choudhury, Subhasree Roy; Karmakar, Surajit; Banik, Naren L.; Ray, Swapan K.

doi:10.1007/s10637-009-9324-7

Cited by 31 publications

(23 citation statements)

References 42 publications

(67 reference statements)

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“…The combination of nutritional factors with anti-cancer drugs has been suggested to be a potential strategy for cancer therapy [17][18][19]33]. In this study, we report for the first time that BI had the potential to enhance the metastasis-inhibitory effect of SF in SK-Hep-1 cells.…”

Section: Discussionmentioning

confidence: 73%

“…Several studies have suggested that nutritional factors may cooperatively or synergistically enhance the effect of anti-cancer drugs to inhibit the metastasis of cancer cells through various mechanisms [17][18][19]. For example, Roy Choudhury et al [19] found that combination of SF and genistein synergistically inhibited angiogenic and survival factors and increased apoptosis in both neuroblastoma SK-N-DZ and SH-SY5Y cell lines. Furthermore, combination therapy may reduce the toxicity of chemotherapy [20].…”

Section: Introductionmentioning

confidence: 99%

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Synergistic effects of the combination of β-ionone and sorafenib on metastasis of human hepatoma SK-Hep-1 cells

Huang

Lyu

2011

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The combination of anti-cancer drugs with nutritional factors is a potential strategy for improving the efficacy of chemotherapy, particularly for hepatocellular carcinoma because its conventional therapies are mostly ineffective. Using a highly invasive hepatoma SK-Hep-1 cell line, we investigated the possible synergistic anti-metastatic efficacy of a combination of sorafenib (SF), a multi-kinase inhibitor, and β-ionone (BI), a precursor of carotenoids. We found that SF (1 μM) in combination with BI (1 μM) synergistically inhibited cell invasion and additively inhibited cell migration, especially at 48 h of incubation. Mechanistically, the combination of SF and BI was found to decrease the protein expression of focal adhesion kinase (FAK) and Rho, and to enhance the protein expression of tissue inhibitor matrix metalloproteinase (TIMP)-1 and TIMP-2. In addition, the combination of SF and BI inhibited the activity of matrix metalloproteinase (MMP)-2 and MMP-9 and decreased the phosphorylation of FAK and of Rac1 proteins. Importantly, SF enhanced the suppressing effect of BI (1-50 μM) on the viability of SK-Hep-1 cells, but not on murine hepatic BNL CL.2 cells, indicating the selective cytotoxicity of this combination on tumor cells. The combination of SF and BI could be a potential therapeutic strategy against human hepatoma cells.

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Section: Discussionmentioning

confidence: 73%

Section: Introductionmentioning

confidence: 99%

Synergistic effects of the combination of β-ionone and sorafenib on metastasis of human hepatoma SK-Hep-1 cells

Huang

Lyu

2011

Invest New Drugs

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“…Cells were re-suspended in PBS, fixed with 70% ethanol, labeled with staining solution (0.05 mg/ml PI, 2 mg/ml RNase A, 0.1% TritonX-100 in PBS), and incubated for 30 min at room temperature (RT) in darkness. DNA content was then analyzed using an Epics XL-MCL Flow Cytometer (Beckman Coulter, Fullerton, CA), as we reported recently [21].…”

Section: Cell Cycle Analysismentioning

confidence: 99%

“…Cells were washed with cold PBS, resuspended in 19 binding buffer (0.1 M HEPES/NaOH, pH 7.4, 1.4 M NaCl, 25 mM CaCl 2 ), stained with Annexin V-FITC/PI, and incubated for 15 min at RT in the darkness. Cells were analyzed for Annexin V-stained apoptotic population using an Epics XL-MCL Flow Cytometer (Beckman Coulter, Fullerton, CA), as per our previous reports [20,21].…”

Section: Flow Cytometric Analysis Of Apoptosismentioning

confidence: 99%

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

et al. 2011

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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.

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Preclinical Models of Pediatric Solid Tumors (Neuroblastoma) and Their Use in Drug Discovery

2011

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Neuroblastoma is the most common pediatric abdominal solid tumor. This aggressive embryonal malignancy of neural crest origin has a peak age of onset of 22 months, and accounts for ~11% of all pediatric cancers and 15% of all pediatric cancer deaths. With current treatment protocols, including high-dose chemotherapy with autologous stem cell transplantation, radiation, and surgery, ~80% of high-risk patients go into remission, although the majority relapse and succumb to therapy-resistant tumors. Long-term survival rates (>5 years) are <50%. Mouse models of neuroblastoma provide clinically relevant tools for studying the growth and metastasis of this aggressive malignancy, and for testing the efficacy of potentially novel therapeutics in vivo. This unit describes an orthotopic murine model of neuroblastoma using cultured human cells that closely mimics the clinical condition in terms of the bulky intra-abdominal tumors and other aspects of metastatic disease. Also described are methods for in vivo imaging and monitoring of tumor growth, and procedures for necropsy and tumor preservation for pathological analysis.

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Synergistic efficacy of sorafenib and genistein in growth inhibition by down regulating angiogenic and survival factors and increasing apoptosis through upregulation of p53 and p21 in malignant neuroblastoma cells having N-Myc amplification or non-amplification

Cited by 31 publications

References 42 publications

Synergistic effects of the combination of β-ionone and sorafenib on metastasis of human hepatoma SK-Hep-1 cells

Synergistic effects of the combination of β-ionone and sorafenib on metastasis of human hepatoma SK-Hep-1 cells

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

Preclinical Models of Pediatric Solid Tumors (Neuroblastoma) and Their Use in Drug Discovery

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