Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0009402 (colorectal cancer)
 53,228 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

GGT catalyses the transfer of gamma-glutamyl residues to amino acids or small peptides. A number of publications report the purification of GGT, the rat kidney enzyme being the best characterized. Bromelain treatment liberates an active form with a molecular weight of 68,000 separable into two nonidentical glycopeptides with molecular weights of 46,000 and 22,000; the latter contains the gamma-glutamyl binding site. GGT is intimately concerned in the synthesis and metabolism of glutathione through the gamma-glutamyl cycle. There is good evidence that this plays a role in the absorption of amino acids from the glomerular filtrate and from the intestinal lumen through a translocation mechanism. Many studies indicate that the GGT content of liver is increased by enzyme-inducing drugs and that this increase is reflected in elevated activity of the enzyme in blood serum. The serum assay has potential in monitoring drug compliance. Increased serum GGT activity encountered in chronic alcoholics seems to be partly due to microsomal enzyme induction. Utility of the assay in detecting alcoholism is controversial, but it is a useful index to compliance with therapy. Dramatic increases in activity are found in many chemically-induced animal tumors, and can be recognized in premalignant cells long before any morphological changes become evident. It has been used as a test for hepatic metastases, but its predictive value has shown a wide range in the hands of many authors. A similar controversy applies to its role in monitoring cancer therapy. Many synthetic substrates have been used to measure serum GGT activity. Currently, L-gamma-glutamyl-p-nitroanilide is the most popular. Males have higher values than females; activity is very high in the neonate and rather low in pregnancy. The most universal application of serum GGT assay is in diagnosis of liver and biliary tract disease. It is widely believed that higher values occur in biliary obstruction than in parenchymal disease. However, the percentage incidence of abnormalities and the overlap of values in individual cases in different disease categories are so great that the enzyme cannot be recommended for this purpose. Isoenzyme analyses have been performed in an attempt to improve the diagnostic specificity of the serum GGT assay. Tissue-specific patterns have not been described, and disease-specific patterns cannot be reproduced with confidence. Whereas exciting advances are being made in understanding the molecular structure, mechanism, and functions of the enzyme it has yet to find a genuinely useful diagnostic role substantiated by a convincing body of scientific data.
CRC Crit Rev Clin Lab Sci 1980
PMID:Structural, functional, and clinical aspects of gamma-glutamyltransferase. 610 63

Advanced colorectal cancer (CRC) survival rates are still low despite advances in cytotoxic and targeted therapies. The development of new effective or alternative therapies is therefore urgently needed. Bromelain, an extract of pineapple, was shown to have anticancer effects, but its mechanisms in CRC have not been fully explored. Therefore, the roles of bromelain in CRC progression were investigated using different CRC cell lines, a zebrafish model, and a xenograft mouse model. The anticancer mechanisms were explored by assessing the role of bromelain in inducing reactive oxygen species (ROS), superoxide, autophagosomes, and lysosomes. The role of bromelain in the induction of apoptosis was also assessed. It was found that bromelain inhibited CRC cell growth in cell lines and tumor growth in the zebrafish and xenograft mouse models. It also induced high levels of ROS and superoxide, plus autophagosome and lysosome formation. High levels of apoptosis were also induced, which were associated with elevated amounts of apoptotic proteins like apoptotic induction factor, Endo G, and caspases-3, -8, and -9 according to a qPCR analysis. In a Western blot analysis, increases in levels of ATG5/12, beclin, p62, and LC3 conversion rates were found after bromelain treatment. Levels of cleaved caspase-3, caspase-8, caspase-9, and poly(ADP ribose) polymerase (PARP)-1 increased after bromelain exposure. This study explored the role of bromelain in CRC while giving insights into its mechanisms of action. This compound can offer a cheap alternative to current therapies.
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PMID:Bromelain inhibits the ability of colorectal cancer cells to proliferate via activation of ROS production and autophagy. 3065 63