Targeting Cancer Cells With the Natural Compound Obtusaquinone
| Autor: | Hawasatu Dumbuya, Bakhos A. Tannous, Lee-Ann Tjon-Kon-Fat, Christian E. Badr, Stephanie Van Hoppe |
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| Rok vydání: | 2013 |
| Předmět: |
Cancer Research
Programmed cell death Immunoblotting Down-Regulation Antineoplastic Agents Breast Neoplasms Context (language use) Biology medicine.disease_cause Article Mice Cell Line Tumor Neoplasms Tumor Cells Cultured medicine Animals Humans Immunoprecipitation Viability assay Cyclohexanones Cancer Neoplasms Experimental Flow Cytometry medicine.disease Glutathione Xenograft Model Antitumor Assays Gene Expression Regulation Neoplastic Oxidative Stress Treatment Outcome Oncology Cinnamates Cell culture Apoptosis Cancer cell Immunology Cancer research Glioblastoma Reactive Oxygen Species Oxidative stress DNA Damage |
| Zdroj: | JNCI: Journal of the National Cancer Institute. 105:643-653 |
| ISSN: | 1460-2105 0027-8874 |
| Popis: | Tumor cells present high levels of oxidative stress. Cancer therapeutics exploiting such biochemical changes by increasing reactive oxygen species (ROS) production or decreasing intracellular ROS scavengers could provide a powerful treatment strategy.To test the effect of our compound, obtusaquinone (OBT), we used several cell viability assays on seven different glioblastoma (GBM) cell lines and primary cells and on 12 different cell lines representing various cancer types in culture as well as on subcutaneous (n = 7 mice per group) and two intracranial GBM (n = 6-8 mice per group) and breast cancer (n = 6 mice per group) tumor models in vivo. Immunoblotting, immunostaining, flow cytometry, and biochemical assays were used to investigate the OBT mechanism of action. Histopathological analysis (n = 2 mice per group) and blood chemistry (n = 2 mice per group) were used to test for any compound-related toxicity. Statistical tests were two-sided.OBT induced rapid increase in intracellular ROS levels, downregulation of cellular glutathione levels and increase in its oxidized form, and activation of cellular stress pathways and DNA damage, subsequently leading to apoptosis. Oxidative stress is believed to be the main mechanism through which this compounds targets cancer cells. OBT was well tolerated in mice, slowed tumor growth, and statistically prolonged survival in GBM tumor models. The ratio of median survival in U251 intracranial model in OBT vs control was 1.367 (95% confidence interval [CI] of ratio = 1.031 to 1.367, P = .008). Tumor growth inhibition was also observed in a mouse breast cancer model (average tumor volume per mouse, OBT vs control: 36.3 vs 200.4mm(3), difference = 164.1mm(3), 95% CI =72.6 to 255.6mm(3), P = .005).Given its properties and efficacy in cancer killing, our results suggest that OBT is a promising cancer therapeutic. |
| Databáze: | OpenAIRE |
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