Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.1.1 (hexokinase)
 5,274 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Jasmonates act as signal transduction intermediates when plants are subjected to environmental stresses such as UV radiation, osmotic shock and heat. In the past few years several groups have reported that jasmonates exhibit anti-cancer activity in vitro and in vivo and induce growth inhibition in cancer cells, while leaving the non-transformed cells intact. Recently, jasmonates were also discovered to have cytotoxic effects towards metastatic melanoma both in vitro and in vivo. Three mechanisms of action have been proposed to explain this anti-cancer activity. The bio-energetic mechanism - jasmonates induce severe ATP depletion in cancer cells via mitochondrial perturbation. Furthermore, methyl jasmonate (MJ) has the ability to detach hexokinase from the mitochondria. Second, jasmonates induce re-differentiation in human myeloid leukemia cells via mitogen-activated protein kinase (MAPK) activity and were found to act similar to the cytokinin isopentenyladenine (IPA). Third, jasmonates induce apoptosis in lung carcinoma cells via the generation of hydrogen peroxide, and pro-apoptotic proteins of the Bcl-2 family. Combination of MJ with the glycolysis inhibitor 2-deoxy-d-glucose (2DG) and with four conventional chemotherapeutic drugs resulted in super-additive cytotoxic effects on several types of cancer cells. Finally, jasmonates have the ability to induce death in spite of drug-resistance conferred by either p53 mutation or P-glycoprotein (P-gp) over-expression. In summary, the jasmonates are anti-cancer agents that exhibit selective cytotoxicity towards cancer cells, and thus present hope for the development of cancer therapeutics.
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PMID:Methyl jasmonate: a plant stress hormone as an anti-cancer drug. 1966 Jul 69

BRAF kinase inhibitors have dramatically affected treatment of BRAF(V600E) (/) (K)-driven metastatic melanoma. Early responses assessed using [(18)F]fluorodeoxyglucose uptake-positron emission tomography (FDG-PET) have shown dramatic reduction of radiotracer signal within 2 weeks of treatment. Despite high response rates, relapse occurs in nearly all cases, frequently at sites of treated metastatic disease. It remains unclear whether initial loss of (18)FDG uptake is due to tumor cell death or other reasons. Here, we provide evidence of melanoma cell volume reduction in a patient cohort treated with BRAF inhibitors. We present data demonstrating that BRAF inhibition reduces melanoma glucose uptake per cell, but that this change is no longer significant following normalization for cell volume changes. We also demonstrate that volume normalization greatly reduces differences in transmembrane glucose transport and hexokinase-mediated phosphorylation. Mechanistic studies suggest that this loss of cell volume is due in large part to decreases in new protein translation as a consequence of vemurafenib treatment. Ultimately, our findings suggest that cell volume regulation constitutes an important physiologic parameter that may significantly contribute to radiographic changes observed in clinic.
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PMID:BRAF Inhibition Decreases Cellular Glucose Uptake in Melanoma in Association with Reduction in Cell Volume. 2594 95

To investigate the role of C16:0 ceramide in melanoma metastatic behavior and glycolysis, five common long-chain ceramides (C16:0, C18:0, C20:0, C22:0, C24:0) were tested in melanocyte and melanoma cell lines by LC-MS. We then treated non-metastatic and metastatic melanoma cells with PDMP and exogenous C16:0 to explore their effects on proliferation, migration, and glycolysis. The long-chain ceramide was also analyzed by LC-MS after treatment. C16:0 ceramide showed the highest levels in melanocyte and melanoma cells, with all melanomas higher than melanocytes. PDMP inhibited malignant behavior and glycolysis in melanoma, and caused the accumulation of intracellular C16:0. Exogenous C16:0 promoted melanoma glycolysis, but not malignant behavior, and decreased intracellular C16:0. Finally, pyruvate kinase (PK), hexokinase (HK), and lactic acid dehydrogenase (LDH) activity, key enzymes in glycolysis, were altered after treatment with PDMP and exogenous C16:0.
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PMID:C16:0 ceramide effect on melanoma malignant behavior and glycolysis depends on its intracellular or exogenous location. 3226 39