β‑hydroxybutyrate does not alter the effects of glucose deprivation on breast cancer cells

Maldonado, Rylee; Talana, Chloe Adrienna; Song, Cassaundra; Dixon, Alyssa M.; Uehara, Kahealani; Weichhaus, Michael

doi:10.3892/ol.2020.12326

Cited by 8 publications

(5 citation statements)

References 63 publications

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“…Chen et al [47] reported that short term glucose deprivation (24 h) in various breast cancer cell lines induced cell death, which was higher in MDA-MB-231 than MCF-7 cells, in part through enhanced AMPK phosphorylation. This was also observed in another report using MCF-7 and T47D cells [48]. We did not see much difference in cell proliferation at 24 h; it was evident at day 4 of glucose starvation in both the cancer lines as well as the normal cells.…”

Section: Discussionsupporting

confidence: 89%

Glucose deprivation reduces proliferation and motility, and enhances the anti-proliferative effects of paclitaxel and doxorubicin in breast cell lines in vitro

2022

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Background Breast cancer chemotherapy with high dose alkylating agents is severely limited by their collateral toxicity to crucial normal tissues such as immune and gut cells. Taking advantage of the selective dependence of cancer cells on high glucose and combining glucose deprivation with these agents could produce therapeutic synergy. Methods In this study we examined the effect of glucose as well as its deprivation, and antagonism using the non-metabolized analogue 2-deoxy glucose, on the proliferation of several breast cancer cell lines MCF7, MDA-MB-231, YS1.2 and pII and one normal breast cell line, using the MTT assay. Motility was quantitatively assessed using the wound healing assay. Lactate, as the end product of anaerobic glucose metabolism, secreted into culture medium was measured by a biochemical assay. The effect of paclitaxel and doxorubicin on cell proliferation was tested in the absence and presence of low concentrations of glucose using MTT assay. Results In all cell lines, glucose supplementation enhanced while glucose deprivation reduced both their proliferation and motility. Lactate added to the medium could substitute for glucose. The inhibitory effects of paclitaxel and doxorubicin were significantly enhanced when glucose concentration was decreased in the culture medium, requiring 1000-fold lesser concentration to achieve a similar degree of inhibition to that seen in glucose-containing medium. Conclusion Our data show that a synergy was obtained by combining paclitaxel and doxorubicin with glucose reduction to inhibit cancer cell growth, which in vivo, might be achieved by applying a carbohydrate-restricted diet during the limited phase of application of chemotherapy; this could permit a dose reduction of the cytotoxic agents, resulting in greater tolerance and lesser side effects.

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Section: Discussionsupporting

confidence: 89%

Glucose deprivation reduces proliferation and motility, and enhances the anti-proliferative effects of paclitaxel and doxorubicin in breast cell lines in vitro

2022

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“…1 G). This is notable as previous literature reports have not shown a significant effect of βHb on breast cancer cell proliferation [ 38 ]. While normal cells display density-dependent inhibition of proliferation, entering quiescence at maximal concentration, cancer cells show no density-dependent inhibition and continue growing even at high cell densities [ 39 ].…”

Section: Discussionsupporting

confidence: 51%

Metabolic alterations and cellular responses to β-Hydroxybutyrate treatment in breast cancer cells

Fulman-Levy,

Cohen-Harazi,

Levi

et al. 2024

Cancer Metab

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Background The ketogenic diet (KD), based on high fat (over 70% of daily calories), low carbohydrate, and adequate protein intake, has become popular due to its potential therapeutic benefits for several diseases including cancer. Under KD and starvation conditions, the lack of carbohydrates promotes the production of ketone bodies (KB) from fats by the liver as an alternative source of metabolic energy. KD and starvation may affect the metabolism in cancer cells, as well as tumor characteristics. The aim of this study is to evaluate the effect of KD conditions on a wide variety of aspects of breast cancer cells in vitro. Methods Using two cancer and one non-cancer breast cell line, we evaluate the effect of β-hydroxybutyrate (βHb) treatment on cell growth, survival, proliferation, colony formation, and migration. We also assess the effect of KB on metabolic profile of the cells. Using RNAseq analysis, we elucidate the effect of βHb on the gene expression profile. Results Significant effects were observed following treatment by βHb which include effects on viability, proliferation, and colony formation of MCF7 cells, and different effects on colony formation of MDA-MB-231 cells, with no such effects on non-cancer HB2 cells. We found no changes in glucose intake or lactate output following βHb treatment as measured by LC-MS, but an increase in reactive oxygen species (ROS) level was detected. RNAseq analysis demonstrated significant changes in genes involved in lipid metabolism, cancer, and oxidative phosphorylation. Conclusions Based on our results, we conclude that differential response of cancer cell lines to βHb treatment, as alternative energy source or signal to alter lipid metabolism and oncogenicity, supports the need for a personalized approach to breast cancer patient treatment.

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“…In a breast cancer study (Dai et al, 2017), researchers cultured MCF-7 and T47D breast cancer cells with different glucose concentrations and found that low glucose concentration significantly inhibited the proliferation of breast cancer cells. Moreover, signal pathway enrichment analysis showed that the Hippo-Yap cell signaling pathway in MCF-7 breast cancer cells was downregulated when the glucose concentration in the culture environment was reduced, whereas the expression of NRF2 pathway-related genes in T47D breast cancer cells was significantly increased (Maldonado et al, 2021). In a recent lung cancer study, researchers found that glucose metabolism disorders may be closely associated with the carcinogenesis of lung cancer, which suggests that glucose metabolism may be a potential therapeutic target for lung cancer (Ding et al, 2019).…”

Section: Glucose Metabolism Reprogramming In Cancer Progressionmentioning

confidence: 99%

Recent Metabolomics Analysis in Tumor Metabolism Reprogramming

Han

Chen

et al. 2021

Front. Mol. Biosci.

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Metabolic reprogramming has been suggested as a hallmark of cancer progression. Metabolomic analysis of various metabolic profiles represents a powerful and technically feasible method to monitor dynamic changes in tumor metabolism and response to treatment over the course of the disease. To date, numerous original studies have highlighted the application of metabolomics to various aspects of tumor metabolic reprogramming research. In this review, we summarize how metabolomics techniques can help understand the effects that changes in the metabolic profile of the tumor microenvironment on the three major metabolic pathways of tumors. Various non-invasive biofluids are available that produce accurate and useful clinical information on tumor metabolism to identify early biomarkers of tumor development. Similarly, metabolomics can predict individual metabolic differences in response to tumor drugs, assess drug efficacy, and monitor drug resistance. On this basis, we also discuss the application of stable isotope tracer technology as a method for the study of tumor metabolism, which enables the tracking of metabolite activity in the body and deep metabolic pathways. We summarize the multifaceted application of metabolomics in cancer metabolic reprogramming to reveal its important role in cancer development and treatment.

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β‑hydroxybutyrate does not alter the effects of glucose deprivation on breast cancer cells

Cited by 8 publications

References 63 publications

Glucose deprivation reduces proliferation and motility, and enhances the anti-proliferative effects of paclitaxel and doxorubicin in breast cell lines in vitro

Glucose deprivation reduces proliferation and motility, and enhances the anti-proliferative effects of paclitaxel and doxorubicin in breast cell lines in vitro

Metabolic alterations and cellular responses to β-Hydroxybutyrate treatment in breast cancer cells

Recent Metabolomics Analysis in Tumor Metabolism Reprogramming

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