β-Caryophyllene Enhances the Transcriptional Upregulation of Cholesterol Biosynthesis in Breast Cancer Cells
| Autor: | Christopher J. Frost, Susan C. Frost, Andrea S Ramirez-Mata, John V. Mathias, Riley O’Donnell, Mam Y. Mboge, Adam Bullock, Julie Davila |
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| Rok vydání: | 2019 |
| Předmět: |
Cell signaling
0303 health sciences Programmed cell death biology Membrane permeability Cholesterol General Medicine Stearoyl-CoA Article Cell biology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine chemistry Downregulation and upregulation 030220 oncology & carcinogenesis HMG-CoA reductase Cancer cell biology.protein Cytotoxic T cell lipids (amino acids peptides and proteins) Cytotoxicity Lipid raft 030304 developmental biology |
| Zdroj: | Curr Top Biochem Res |
| DOI: | 10.1101/569558 |
| Popis: | β-caryophyllene (BCP) exhibits anti-proliferative properties in cancer cells. Here, we examine the hypothesis that BCP induces membrane remodeling. Our data show that high concentrations of BCP increase membrane permeability of human breast cells (hBrC) causing detachment and cell death. At a sub-lethal concentration of BCP, we show that BCP induces a striking upregulation of genes involved in cholesterol biosynthesis, including the gene that encodes for HMGCoA reductase (HMGCR), the rate-determining step in cholesterol biosynthesis. In addition, stearoyl-CoA desaturase (SCD) is also upregulated which would lead to the enhanced formation of monounsaturated fatty acids, specifically oleate and palmitoleate from stearoyl CoA and palmitoyl CoA, respectively. These fatty acids are major components of membrane phospholipids and cholesterol esters. Together, these data suggest that cells respond to BCP by increasing the synthesis of components found in membranes. These responses could be viewed as a repair mechanism and/or as a mechanism to mount resistance to the cytotoxic effect of BCP. Blocking HMGCR activity enhances the cytotoxicity of BCP, suggesting that BCP may provide an additional therapeutic tool in controlling breast cancer cell growth. |
| Databáze: | OpenAIRE |
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