Multi-dimensional roles of ketone bodies in cancer biology: Opportunities for cancer therapy

Feng, Suhua; Wang, Huan; Liu, Jiali; Aa, Jiye; Zhou, Fang; Wang, Guangji

doi:10.1016/j.phrs.2019.104500

Cited by 45 publications

(40 citation statements)

References 75 publications

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“…Ketone metabolism has gradually become a hot topic of molecular and clinical cancer research (6)(7)(8). During fasting, the liver can rapidly oxidize and decompose fatty acids to form acetyl-CoA, further synthesize ketone bodies, thereby providing a fast and efficient energy supply to important energy-consuming organs such as brain, muscle, and kidney.…”

Section: Introductionmentioning

confidence: 99%

Dysregulation of Ketone Body Metabolism Is Associated With Poor Prognosis for Clear Cell Renal Cell Carcinoma Patients

et al. 2019

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Kidney is an important organ for ketone body metabolism. However, the role of abnormal ketone metabolism and its possible function in tumorigenesis of clear cell renal cell carcinoma (ccRCC) have not yet been elucidated. Three differentially expressed key enzymes involved in ketone body metabolism, ACAT1, BDH2, and HMGCL, were screened out between ccRCC and normal kidney tissues using the GEO and TCGA databases.We confirmed that the transcription and protein expression of ACAT1, BDH2, and HMGCL were significantly lower in ccRCC by real-time RT-PCR and IHC assays. Those patients with lower expression of these three genes have a worse outcome. In addition, we demonstrated that ectopic expression of each of these genes inhibited the proliferation of ccRCC cells. The overexpressed ACAT1 and BDH2 genes remarkably impeded the migratory and invasive capacity of ccRCC cells. Furthermore, exogenous β-hydroxybutyrate suppressed the growth of ccRCC cells in vitro in a dose-dependent manner. Our findings suggest that ACAT1, BDH2, and HMGCL are potential tumor suppressor genes, and constitute effective prognostic biomarkers for ccRCC. Ketone body metabolism might thus be a promising target in a process for developing novel therapeutic approaches to treat ccRCC.

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Section: Introductionmentioning

confidence: 99%

Dysregulation of Ketone Body Metabolism Is Associated With Poor Prognosis for Clear Cell Renal Cell Carcinoma Patients

et al. 2019

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“…Upon crude IL-GPE exposure, HT29 cells showed an alteration of ketone bodies by upregulating the acetone. Mitochondrial dysfunction is responsible for many cancer metabolic deficiencies and prevents the use of ketone bodies to produce energy in cancer cells (Feng et al, 2019). Previous experiments have demonstrated that, unlike normal tissue, tumour cells can not efficiently utilise ketone bodies to produce energy.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of metabolomics behavior of human colon cancer HT29 cell lines treated with ionic liquid graviola fruit pulp extract

Daddiouaissa

Amid

Sani

et al. 2021

Journal of Ethnopharmacology

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Medicinal plants have been used by indigenous people across the world for centuries to help individuals preserve their wellbeing and cure diseases. Annona muricata L. (Graviola) which is belonging to the Annonaceae family has been traditionally used due to its medicinal abilities including antimicrobial, anti-inflammatory, antioxidant and cancer cell growth inhibition. Graviola is claimed to be a potential antitumor due to its selective cytotoxicity against several cancer cell lines. However, the metabolic mechanism information underlying the anticancer activity remains limited. Aim of the study: This study aimed to investigate the effect of ionic liquid-Graviola fruit pulp extract (IL-GPE) on the metabolomics behavior of colon cancer (HT29) by using an untargeted GC-TOFMS-based metabolic profiling. Materials and methods: Multivariate data analysis was used to determine the metabolic profiling, and the ingenuity pathway analysis (IPA) was used to predict the altered canonical pathways after treating the HT29 cells with crude IL-GPE and Taxol (positive control). Results: The principal components analysis (PCA) identified 44 metabolites with the most reliable factor loading, and the cluster analysis (CA) separated three groups of metabolites: metabolites specific to the non-treated HT29 cells, metabolites specific to the treated HT29 cells with the crude IL-GPE and metabolites specific to Taxol treatment. Pathway analysis of metabolomic profiles revealed an alteration of many metabolic pathways, including amino acid metabolism, aerobic glycolysis, urea cycle and ketone bodies metabolism that contribute to energy metabolism and cancer cell proliferation. Conclusion:The crude IL-GPE can be one of the promising anticancer agents due to its selective inhibition of energy metabolism and cancer cell proliferation.

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“…Glucose dependency and lactate production are recognized as two key features related to the aggressive capacity and invasive potential of cancer cells (20). Normal cells readily use ketones as an alternate energy source and induce a shift in cellular energy supply from glucose to fatty acids and ketones to protect against hypoglycemia when ketone body levels rise (21). Cancer cells are incapable of ketone body metabolism due to their acquired metabolic inflexibility (22).…”

Section: The Ketogenic Diet (Kd)mentioning

confidence: 99%

“…The side effects caused by the KD, including constipation, fatigue, leg cramps, vomiting, lack of energy, and hunger, are reversible (67,68). In addition, the KD should be low in proteins (mainly vegetable proteins) and carbohydrates (non-starchy vegetables) and high in lipids [mainly unprocessed vegetable oils rich in polyunsaturated fatty acids (PUFAs)] (16,21,69). It is worth noting that the classic artificial KD may be deficient in vitamins and minerals (70).…”

Section: The Ketogenic Diet (Kd)mentioning

confidence: 99%

Beneficial Diets and Pancreatic Cancer: Molecular Mechanisms and Clinical Practice

Zhang

Yang

et al. 2021

Front. Oncol.

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Pancreatic cancer (PC) is a malignant tumor with high invasiveness, easy metastatic ability, and chemoresistance. Patients with PC have an extremely low survival rate due to the difficulty in early diagnosis. It is estimated that nearly 90% of PC cases are caused by environmental risk factors. Approximately 50% of PC cases are induced by an unhealthy diet, which can be avoided. Given this large attribution to diet, numerous studies have assessed the relationship between various dietary factors and PC. This article reviews three beneficial diets: a ketogenic diet (KD), a Mediterranean diet (MD), and a low-sugar diet. Their composition and impact mechanism are summarized and discussed. The associations between these three diets and PC were analyzed, and we aimed to provide more help and new insights for the prevention and treatment of PC.

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Multi-dimensional roles of ketone bodies in cancer biology: Opportunities for cancer therapy

Cited by 45 publications

References 75 publications

Dysregulation of Ketone Body Metabolism Is Associated With Poor Prognosis for Clear Cell Renal Cell Carcinoma Patients

Dysregulation of Ketone Body Metabolism Is Associated With Poor Prognosis for Clear Cell Renal Cell Carcinoma Patients

Evaluation of metabolomics behavior of human colon cancer HT29 cell lines treated with ionic liquid graviola fruit pulp extract

Beneficial Diets and Pancreatic Cancer: Molecular Mechanisms and Clinical Practice

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