γ-Tocotrienol Suppression of the Warburg Effect Is Mediated by AMPK Activation in Human Breast Cancer Cells
Autor: | Venkateshwara Dronamraju, Paul W. Sylvester, Baher A. Ibrahim, Karen P. Briski |
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Rok vydání: | 2019 |
Předmět: |
musculoskeletal diseases
0301 basic medicine Cancer Research animal structures Medicine (miscellaneous) Breast Neoplasms AMP-Activated Protein Kinases 03 medical and health sciences 0302 clinical medicine Cell Line Tumor Humans Vitamin E Glycolysis Chromans Phosphorylation Protein kinase B Cell Proliferation 030109 nutrition & dietetics Nutrition and Dietetics integumentary system Dose-Response Relationship Drug Kinase Chemistry Forkhead Box Protein O3 AMPK Warburg effect Enzyme Activation Gene Expression Regulation Neoplastic Metabolic pathway Glucose Oncology Anaerobic glycolysis 030220 oncology & carcinogenesis Cancer cell Cancer research Female Proto-Oncogene Proteins c-akt |
Zdroj: | Nutrition and cancer. 71(7) |
ISSN: | 1532-7914 |
Popis: | Cancer cell metabolism is characterized by aerobic glycolysis or the "Warburg effect". Enhanced Akt signaling is associated with activation of various downstream enzymes involved in the glycolytic process, whereas activation of 5'-AMP-activated kinase (AMPK) acts to terminate energy expending mechanisms and decrease glycolytic enzyme expression. Studies were conducted to determine if the anticancer effects of γ-tocotrienol, are mediated through a suppression in aerobic glycolysis. Results show that treatment with 0-7 μM γ-tocotrienol throughout a 4-day culture period resulted in a dose-responsive increase in AMPK activation, and corresponding decrease in Akt activity in human MCF-7 and MDA-MB-231 breast cancer cells. γ-Tocotrienol treatment was also found to induce a dose-responsive decrease in phosphorylated-Fox03 (inactivated), a transcription factor that acts to inhibit in the levels of glycolytic enzyme, and this decrease was associated with a reduction in glycolytic enzyme levels and activity, as well as glucose consumption in these cells. PCR microarray analysis shows that γ-tocotrienol treatment decreases the expression of genes associate with metabolic signaling and glycolysis in MCF-7 and MDA-MB-231 breast cancer cells. In summary, these findings demonstrate that the anticancer effects of γ-tocotrienol are mediated, at least in part, by a suppression in the Warburg effect. |
Databáze: | OpenAIRE |
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