Acetate as a Metabolic and Epigenetic Modifier of Cancer Therapy

Jaworski, Diane M.; Namboodiri, Aryan M.A.; Moffett, John R.

doi:10.1002/jcb.25305

Cited by 56 publications

(44 citation statements)

References 86 publications

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“…Glucose carbon is primarily directed through glycolysis, the pentose phosphate pathway, and lipogenesis, which together provide intermediates necessary for tumor biomass expansion (Grabacka et al, 2016; Shukla et al, 2014; Yoshii et al, 2015). Adaptation of cancer cells to glucose deprivation occurs through the ability to exploit alternative fuel sources, including acetate, glutamine, and aspartate (Jaworski et al, 2016; Sullivan et al, 2015). For example, restricted access to pyruvate reveals the ability of cancer cells to convert glutamine into acetyl-CoA by carboxylation, maintaining both energetic and anabolic needs (Yang et al, 2014).…”

Section: Ketone Bodies In Cancer Biologymentioning

confidence: 99%

Multi-dimensional Roles of Ketone Bodies in Fuel Metabolism, Signaling, and Therapeutics

2017

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Ketone body metabolism is a central node in physiological homeostasis. In this review, we discuss how ketones serve discrete fine-tuning metabolic roles that optimize organ and organism performance in varying nutrient states, and protect from inflammation and injury in multiple organ systems. Traditionally viewed as metabolic substrates enlisted only in carbohydrate restriction, recent observations underscore the importance of ketone bodies as vital metabolic and signaling mediators when carbohydrates are abundant. Complementing a repertoire of known therapeutic options for diseases of the nervous system, prospective roles for ketone bodies in cancer have arisen, as have intriguing protective roles in heart and liver, opening therapeutic options in obesity-related and cardiovascular disease. Controversies in ketone metabolism and signaling are discussed to reconcile classical dogma with contemporary observations.

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Section: Ketone Bodies In Cancer Biologymentioning

confidence: 99%

Multi-dimensional Roles of Ketone Bodies in Fuel Metabolism, Signaling, and Therapeutics

2017

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“…The ketone body βHB has traditionally been thought of as simply a metabolic substrate that replaces glucose during the KD, fasting or exercise; however, the effects of increased ketones go beyond simple considerations of energy availability (Newman and Verdin, 2014; Jaworski et al, 2016). In vitro investigations demonstrated that βHB is able to recapitulate, in part, the in vivo effects of the full KD (Skinner et al, 2009; Rossi et al, 2015).…”

Section: β-Hydroxybutyrate As An Anti-cancer Agentmentioning

confidence: 99%

Tumor Metabolism, the Ketogenic Diet and β-Hydroxybutyrate: Novel Approaches to Adjuvant Brain Tumor Therapy

Woolf

Syed

Scheck

2016

Front. Mol. Neurosci.

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Malignant brain tumors are devastating despite aggressive treatments such as surgical resection, chemotherapy and radiation therapy. The average life expectancy of patients with newly diagnosed glioblastoma is approximately ~18 months. It is clear that increased survival of brain tumor patients requires the design of new therapeutic modalities, especially those that enhance currently available treatments and/or limit tumor growth. One novel therapeutic arena is the metabolic dysregulation that results in an increased need for glucose in tumor cells. This phenomenon suggests that a reduction in tumor growth could be achieved by decreasing glucose availability, which can be accomplished through pharmacological means or through the use of a high-fat, low-carbohydrate ketogenic diet (KD). The KD, as the name implies, also provides increased blood ketones to support the energy needs of normal tissues. Preclinical work from a number of laboratories has shown that the KD does indeed reduce tumor growth in vivo. In addition, the KD has been shown to reduce angiogenesis, inflammation, peri-tumoral edema, migration and invasion. Furthermore, this diet can enhance the activity of radiation and chemotherapy in a mouse model of glioma, thus increasing survival. Additional studies in vitro have indicated that increasing ketones such as β-hydroxybutyrate (βHB) in the absence of glucose reduction can also inhibit cell growth and potentiate the effects of chemotherapy and radiation. Thus, while we are only beginning to understand the pluripotent mechanisms through which the KD affects tumor growth and response to conventional therapies, the emerging data provide strong support for the use of a KD in the treatment of malignant gliomas. This has led to a limited number of clinical trials investigating the use of a KD in patients with primary and recurrent glioma.

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“…As a donor of an acetyl group, acetyl CoA is also dynamically associated with the acetylation of protein, which modifies their functions [11]. Therefore, maintenance of the cellular acetyl CoA pool is essential for the regulation of various cellular processes, including cell transformation and development [12]. For rapidly dividing or metastatic cancer cells, acetyl CoA is particularly important [13].…”

Section: Introductionmentioning

confidence: 99%

Acetyl-CoA Synthetase 2 Promotes Cell Migration and Invasion of Renal Cell Carcinoma by Upregulating Lysosomal-Associated Membrane Protein 1 Expression

Guo

Gui

2018

Cell Physiol Biochem

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Background/Aims: Reprogramming energy metabolism is an emerging hallmark of many cancers, and this alteration is especially evident in renal cell carcinomas (RCCs). However, few studies have been conducted on lipid metabolism. This study investigated the function and mechanism of lipid metabolism-related acetyl-CoA synthetase 2 (ACSS2) in RCC development, cell migration and invasion. Methods: Quantitative real-time PCR (qRT-PCR) was used to determine the expression of ACSS2 in cancer tissue and adjacent tissue. The inhibition of ACSS2 expression was achieved by RNA interference, which was confirmed by qRT-PCR and Western blotting. Cell proliferation and apoptosis were detected by a CCK8 assay and a flow cytometry analysis, respectively. Cell migration and invasion were determined by the scratch and transwell assays. Following the knockdown of ACSS2 expression, the expression of the autophagy-related factor LAMP1 was measured by qRT-PCR and Western blotting. Results: Compared to adjacent tissues, ACSS2 expression was upregulated in RCC cancer tissues and positively correlated with metastasis. Inhibition of ACSS2 had no effect on RCC cell proliferation or apoptosis. However, decreased ACSS2 expression was found to inhibit RCC cell migration and invasion. ACSS2 was determined to promote the expression of LAMP1, which can also promote cell migration. This pathway may be considered a potential mechanism through which ACSS2 participates in RCC development. Conclusion: These data suggest that ACSS2 is an important factor for promoting RCC development and is essential for cell migration and invasion, which it promotes by increasing the expression of LAMP1. Taken together, these findings reveal a potential target for the diagnosis and treatment of RCC.

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Acetate as a Metabolic and Epigenetic Modifier of Cancer Therapy

Cited by 56 publications

References 86 publications

Multi-dimensional Roles of Ketone Bodies in Fuel Metabolism, Signaling, and Therapeutics

Multi-dimensional Roles of Ketone Bodies in Fuel Metabolism, Signaling, and Therapeutics

Tumor Metabolism, the Ketogenic Diet and β-Hydroxybutyrate: Novel Approaches to Adjuvant Brain Tumor Therapy

Acetyl-CoA Synthetase 2 Promotes Cell Migration and Invasion of Renal Cell Carcinoma by Upregulating Lysosomal-Associated Membrane Protein 1 Expression

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