Abstract
Background:Altered metabolism is one of the hallmarks of the cancer cells which reciprocally interrelate with epigenetic processes, such as post-translational histone modifications to maintain their desired gene expression profiles. The role of beta-hydroxybutyrate as a ketone body in cancer cell biology and histone modifications are reported. The present study aimed to evaluate the impacts of long-term metabolic reprogramming via glucose restriction and beta-hydroxybutyrate treatment on histone acetylation and butyrylation in MDA-MB231 cells as a model of triple negative stem-like breast cancer. Methods:For long-term treatment, cells were set up in three groups receiving DMEM with restricted glucose (250 mg/L), DMEM with restricted glucose but enriched with five millimolar beta-hydroxybutyrate and DMEM with standard glucose (1g\\L) and investigated for a month. Histone modifications, including H3 acetylation and butyrylation, were investigated by immunoblotting after an acid extraction of the histone proteins. Results and Conclusion:Neither beta-hydroxybutyrate enrichment nor glucose restriction elicited a significant effect on the butyrylation or acetylation level of histone H3 upon a long-term treatment. Metabolic plasticity of cancer cells, mainly stem-like triple negative breast cancer cells alleviate or neutralize the impact of long-term metabolic reprogramming via restriction of glucose and histone modifications enrichment. These results shed new light upon the mechanism of controversial efficacy of ketogenic diets in clinical trials.
Highlights
Cancer is still one of the leading causes of death worldwide, and breast cancer is one of the most common types of cancer in the well-developed countries, but over the past 30 years, the trend of breast cancer deaths in developing countries has been increasing (Torre et al, 2016)
The present study aimed to evaluate the impacts of long-term metabolic reprogramming via glucose restriction and beta-hydroxybutyrate treatment on histone acetylation and butyrylation in MDA-MB231 cells as a model of triple negative stem-like breast cancer
Histone butyrylation is a significant histone modification that may regulate the expression of specific genes
Summary
Cancer is still one of the leading causes of death worldwide, and breast cancer is one of the most common types of cancer in the well-developed countries, but over the past 30 years, the trend of breast cancer deaths in developing countries has been increasing (Torre et al, 2016). Breast cancer, based on the expression of estrogen and progesterone receptors, and HER-2, are divided into subgroups in which the subgroup lacking those markers are called triple negative breast cancer (TNBC). The present study aimed to evaluate the impacts of long-term metabolic reprogramming via glucose restriction and beta-hydroxybutyrate treatment on histone acetylation and butyrylation in MDA-MB231 cells as a model of triple negative stem-like breast cancer. Metabolic plasticity of cancer cells, mainly stem-like triple negative breast cancer cells alleviate or neutralize the impact of long-term metabolic reprogramming via restriction of glucose and histone modifications enrichment. These results shed new light upon the mechanism of controversial efficacy of ketogenic diets in clinical trials
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