Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glioblastoma (GBM) is the most aggressive type of brain tumor and shows very poor prognosis. Here, using genome-wide methylation analysis, we show that G-CIMP+ and G-CIMP-subtypes enrich distinct classes of biological processes. One of the hypermethylated genes in GBM, ULK2, an upstream autophagy inducer, was found to be down-regulated in GBM. Promoter hypermethylation of ULK2 was confirmed by bisulfite sequencing. GBM and glioma cell lines had low levels of ULK2 transcripts, which could be reversed upon methylation inhibitor treatment. ULK2 promoter methylation and transcript levels showed significant negative correlation. Ectopic overexpression of ULK2-induced autophagy, which further enhanced upon nutrient starvation or temozolomide chemotherapy. ULK2 also inhibited the growth of glioma cells, which required autophagy induction as kinase mutant of ULK2 failed to induce autophagy and inhibit growth. Furthermore, ULK2 induced autophagy and inhibited growth in Ras-transformed immortalized Baby Mouse Kidney (iBMK) ATG5(+/+) but not in autophagy-deficient ATG5(-/-) cells. Growth inhibition due to ULK2 induced high levels of autophagy under starvation or chemotherapy utilized apoptotic cell death but not at low levels of autophagy. Growth inhibition by ULK2 also appears to involve catalase degradation and reactive oxygen species generation. ULK2 overexpression inhibited anchorage independent growth, inhibited astrocyte transformation in vitro and tumor growth in vivo. Of all autophagy genes, we found ULK2 and its homologue ULK1 were only down-regulated in all grades of glioma. Thus these results altogether suggest that inhibition of autophagy by ULK1/2 down-regulation is essential for glioma development.
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PMID:Methylation silencing of ULK2, an autophagy gene, is essential for astrocyte transformation and tumor growth. 2492 41

Influencing cancer metabolism by lifestyle changes is an attractive strategy as - if effective - exercise-induced problems may be less severe than those induced by classical anti-cancer therapies. Pursuing this idea, clinical trials evaluated the benefit of e.g. different diets such as the ketogenic diet, intermittent caloric restriction and physical exercise (PE) in the primary and secondary prevention of different cancer types. PE proved to be beneficial in the context of breast and colon cancer.Glioblastoma has a dismal prognosis, with an average overall survival of about one year despite maximal safe resection, concomitant radiochemotherapy with temozolomide followed by adjuvant temozolomide therapy. Here, we focused on the influence of PE as an isolated and adjuvant treatment in murine GB therapy.PE did not reduce toxic side effects of chemotherapy in mice administered in a dose escalating scheme as shown before for starvation. Although regular treadmill training on its own had no obvious beneficial effects, its combination with temozolomide was beneficial in the treatment of glioblastoma-bearing mice. As PE might partly act through the induction of reactive oxygen species, dihydroartemisinin - an approved anti-malarial drug which induces oxidative stress in glioma cells - was further evaluated in vitro and in vivo. Dihydroartemisinin showed anti-glioma activity by promoting autophagy, reduced the clonogenic survival and proliferation capacity of glioma cells, and prolonged the survival of tumor bearing mice. Using the reactive oxygen species scavenger n-acetyl-cysteine these effects were in part reversible, suggesting that dihydroartemisinin partly acts through the generation of reactive oxygen species.
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PMID:Slowing down glioblastoma progression in mice by running or the anti-malarial drug dihydroartemisinin? Induction of oxidative stress in murine glioblastoma therapy. 2744 60

Glioblastoma is the deadliest neoplasm with the worst 5-year survival rate among all human cancers. Autophagy promotes autophagic cell death or blocks the induction of apoptosis in eukaryotic cells. Here, we investigated whether varying levels of autophagic flux in glioblastoma lead to different efficacies of curcumin treatment using U87MG and A172 human glioblastoma cells. The number of LC3 puncta, the number of cells with LC3 puncta and the level of LC3 II, Atg5 and Atg7 protein were higher in U87MG cells compared with A172 cells. When the cells were incubated with curcumin for 24 or 48 h, the percentage of cell death was higher in A172 cells compared with U87MG cells. Although the level of LC3 was lower, that of curcumin-induced LC3 was higher, in A172 cells than in U87MG cells. The relative increases in cell death and LC3-mediated autophagy were greater under serum starvation in A172 cells compared with U87MG cells. Curcumin-induced A172 cell death was reduced by serum starvation. When both types of cells were transfected with LC3-GFP, the percentage of cell death was higher in A172 cells than that in U87MG cells. Taken together, the data demonstrate that curcumin-mediated tumor cell death is regulated by the basal level of autophagic flux in different glioblastoma cells. This suggests that prior to the use of various curcumin therapeutics, the level of basal or induced autophagic flux should be carefully examined in tumor cells for the best efficacy.
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PMID:Curcumin-induced cell death depends on the level of autophagic flux in A172 and U87MG human glioblastoma cells. 3217 47