Novel molecular mechanisms of antitumor action of dichloroacetate against T cell lymphoma: Implication of altered glucose metabolism, pH homeostasis and cell survival regulation

Kumar, Ajay; Kant, Shri; Singh, Sukh Mahendra

doi:10.1016/j.cbi.2012.06.005

Cited by 58 publications

(46 citation statements)

References 51 publications

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“…ALT catalyses the conversion of alanine to pyruvate and glutamate and is released in a similar manner. Elevated levels of serum enzymes are indicative of cellular leakage and loss of functional integrity of cell membrane in the liver [9]. A similar significant decrease in AST, ALT, and ALP was observed by Santhi and Annapoorani [10] by the administration of silymarin to carbon tetrachloride (CCl 4 ) induced hepatotoxicity in mice.…”

Section: Discussionsupporting

confidence: 52%

Anticancer Activity of Plant Protein Against Dalton’s Lymphoma Ascites Tumor Cell Lines

Srilatha¹,

Santhi²,

Annapurani³

2016

Asian J Pharm Clin Res

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Objective: Tabernaemontana divaricata (Td) is commonly used plants for the treatment of inflammatory, anticancer, and diabetics. The main objective of this study is to assess the antitumor and antioxidant activity of Td in mice model. Methods:Antitumor activity of TdPf extract (52 µg/ml) is evaluated against Dalton's lymphoma ascites (DLA) tumor mice. After 24 hrs of tumor inoculation, the extract is administered daily for 15 and 60 days. After administration of the lost dose followed by 18 hrs fasting, mice are sacrificed for observation of antitumor activity. Antitumor activity is assessed by monitoring the liver marker enzyme, lipid peroxidation effect on antioxidant enzyme levels, and histopathological evidence. Results:The results showed that the protein extract of Td animals restored the antioxidant enzymes when compared to the mice of the DLA control group. Conclusion:The findings indicate that the extract of plant protein has antitumor activity by preventing the lipid peroxidation and thereby promoting the antioxidant systems in DLA induced mice. And hence, it is evident that these extract could be a natural anticancer agent for the human health.

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Section: Discussionsupporting

confidence: 52%

Anticancer Activity of Plant Protein Against Dalton’s Lymphoma Ascites Tumor Cell Lines

Srilatha¹,

Santhi²,

Annapurani³

2016

Asian J Pharm Clin Res

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“…Another compound--redox-silent vitamin E analog α-tocopheryl succinate (α-TOS)--with known antiproliferative effects, has been found to target the UbQ binding site of complex II [196] and shown to be effective in several experimental cancers in vitro and in vivo with no toxicity to normal cells [197][198][199][200]. The other possibility of treatment is inhibition of glycolysis by small molecule inhibitors of GLUT1 [201,202] or its reversion using dichloroacetate (DCA) [203,204] or 3-bromopyruvate (3BP) [205][206][207]. Activation of mitochondrial respiration can also be induced by downregulation of LDH by small interfering ribonucleic acid (siRNA), which prevents conversion of pyruvate to lactate and, as a result, allows for the entry of pyruvate into the mitochondria in order to fuel the TCA cycle and OXPHOS [208].…”

Section: Conclusion and Future Therapeutic Perspectivesmentioning

confidence: 99%

Pheochromocytoma: Gasping for Air

2015

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There has been increasing evidence that pseudohypoxia--a phenomenon that we refer to as "gasping for air"--along with mitochondrial enzyme dysregulation play a crucial role in tumorigenesis, particularly in several hereditary pheochromocytomas (PHEOs) and paragangliomas (PGLs). Alterations in key tricarboxylic acids (TCA) cycle enzymes (SDH, FH, MDH2) have been shown to induce pseudohypoxia via activation of the hypoxia-inducible transcription factor (HIF) signaling pathway that is involved in tumorigenesis, invasiveness, and metastatic spread, including an association with resistance to various cancer therapies and worse prognosis. This review outlines the ongoing story of the pathogenesis of hereditary PHEOs/PGLs, showing the unique and most updated evidence of TCA cycle dysregulation that is tightly linked to hypoxia signaling.

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“…Growth medium was added for 20 hours in the absence or presence of imatinib (5-25 µmol/L) 28 or dichloroacetate (10-50 mmol/L). 29 The bromodeoxyuridine incorporation assay was performed according to the manufacturer's instructions (Roche Diagnostics).…”

Section: Proliferation Assaymentioning

confidence: 99%

Heterogeneity in Lung ¹⁸ FDG Uptake in Pulmonary Arterial Hypertension

et al. 2013

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P ulmonary arterial hypertension (PAH) is a disease of progressive vascular remodeling characterized by dysregulated growth of pulmonary vascular cells and inflammation. [1][2][3][4] In the search for new medicines, the focus is moving toward therapies targeting these mechanisms, drawing on approved oncology interventions, such as tyrosine kinase inhibitors (eg, imatinib) 5,6 and metabolic modulators (eg, dichloroacetate), 7,8 and antiinflammatory treatments. 9 The evaluation of these antiremodeling and anti-inflammatory strategies in PAH patients poses a considerable challenge that may hamper their development. Background-Pulmonary arterial hypertension (PAH) is a disease of progressive vascular remodeling, characterizedby dysregulated growth of pulmonary vascular cells and inflammation. A prevailing view is that abnormal cellular metabolism, notably aerobic glycolysis that increases glucose demand, underlies the pathogenesis of PAH. Increased lung glucose uptake has been reported in animal models. Few data exist from patients with PAH. Methods and Results-Dynamic positron emission tomography imaging with fluorine-18-labeled 2-fluoro-2-deoxyglucose ( Clinical Perspective on p 1224Noninvasive molecular imaging with the use of positron emission tomography (PET) offers enormous potential for monitoring cellular and biochemical events in otherwise inaccessible tissue and has been used in oncology to assess antiproliferative therapeutics. Specifically, fluorine-18-labeled 2-fluoro-2-deoxyglucose ( 18 FDG), a glucose analogue, is widely used for the detection and staging of a variety of malignant lesions and can provide a quantitative assessment of response to treatment.10-13 18 FDG PET exploits the "Warburg effect," 14,15 the observation that many cancers use aerobic cytoplasmic glycolysis as opposed to mitochondrial glucose oxidation as a major energy source, a process that requires increased cellular glucose uptake.Aerobic glycolysis is also a characteristic of nonmalignant proliferating cells and is observed in human pulmonary endothelial cells isolated and cultured from idiopathic PAH (IPAH) patient lungs, 16 as well as in pulmonary arterial smooth muscle cells from rodent PAH models.17 Lung parenchymal glucose uptake, measured by 18 FDG PET, has been reported to be increased in IPAH patients compared with healthy controls. 16,18 Recently, Marsboom et al 19 showed an increased lung 18 FDG PET signal in animal PAH models that is reduced by treatment with imatinib and dichloroacetate. These data provide the foundation for further investigation of the utility of 18 FDG PET as a tool in the assessment of patients with PAH. We set out to explore 3 questions: (1) the utility of dynamic 18 FDG PET acquisition in discriminating between PAH patients and healthy controls; (2) the feasibility of 18 FDG PET in tracking the pathology of pulmonary hypertension in in vivo PAH models and their response to treatment; and (3) the impact of treatments on cellular 18 FDG uptake with the use of IPAH-derived cells in vitro. Our da...

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Novel molecular mechanisms of antitumor action of dichloroacetate against T cell lymphoma: Implication of altered glucose metabolism, pH homeostasis and cell survival regulation

Cited by 58 publications

References 51 publications

Anticancer Activity of Plant Protein Against Dalton’s Lymphoma Ascites Tumor Cell Lines

Anticancer Activity of Plant Protein Against Dalton’s Lymphoma Ascites Tumor Cell Lines

Pheochromocytoma: Gasping for Air

Heterogeneity in Lung ¹⁸ FDG Uptake in Pulmonary Arterial Hypertension

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Novel molecular mechanisms of antitumor action of dichloroacetate against T cell lymphoma: Implication of altered glucose metabolism, pH homeostasis and cell survival regulation

Cited by 58 publications

References 51 publications

Anticancer Activity of Plant Protein Against Dalton’s Lymphoma Ascites Tumor Cell Lines

Anticancer Activity of Plant Protein Against Dalton’s Lymphoma Ascites Tumor Cell Lines

Pheochromocytoma: Gasping for Air

Heterogeneity in Lung 18 FDG Uptake in Pulmonary Arterial Hypertension

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Heterogeneity in Lung ¹⁸ FDG Uptake in Pulmonary Arterial Hypertension