Possible roles of excess tryptophan metabolites in cancer

Abstract

Tryptophan is metabolized through serotonin, indole, and kynurenine (KN) pathways. Uptake of an excess amount of tryptophan accompanied with vitamin B6 deficiency may result in the accumulation of higher concentrations of metabolites mainly from the KN pathways in the bladder. These metabolites could interact with nitrite to become mutagenic nitrosamines. They could be a promoter in the initiator-promoter model of carcinogenesis. They produced bladder cancer when implanted in the bladder. They also interact with transition metals copper or iron to form reactive radicals or reactive oxygen species (ROS). Some metabolites, 3-hydroxy-anthranilic acid, were autooxidized to mutagenic cinnabarinic and anthranilyl radical intermediates. These radical intermediates could also be ligands that interact with aryl hydrocarbon receptor (AhR) and induce xenobiotic metabolizing enzymes (XMEs) to metabolize contaminated carcinogens. When tryptophan is exposed to either visible or UV light, a photoproduct of 6-formylindolo[3,2b]-carbazole is formed, which has a very high affinity for the AhR that plays a role in carcinogenesis. This review gives an insight into various mechanisms through which tryptophan metabolites cause carcinogenesis. It could be concluded that tryptophan metabolites play a complementary role in promoting carcinogenesis along with carcinogens like aflatoxin, CCl(4) , 2-acetylaminofluorene, 4-aminobiphenyl, 2-naphthylamine, or N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide. The underlying mechanisms could be their autoxidation, exposure to either visible or UV light, interaction with nitrite or transition metals to form reactive intermediates, serving as ligands to interact with an AhR that is known to play a role in carcinogenesis through induction of XMEs. Further research is warranted.Environ.

Prostate cancer, tumor immunity and a renewed sense of optimism in immunotherapy

“…While in transplantable models both treatments were alone sufficient to delay tumor growth, in the TRAMP model, neither 1-MT nor anti-CD25 antibodies or their combination impacted on disease progression and T-cell tolerance associated with tumor growth [82]. All together, our data [82] and those reported by Kallberg et al [151] suggest that IDO has a more relevant direct effect on tumor cells [152], which is not fully inhibited by 1-MT. IDO induces expression of a novel tryptophan transporter in mouse and human tumor cells that is responsible for 50% of the tryptophan uptake [153].…”

Raman spectroscopic characterization of urine of normal and oral cancer subjects

“…[59][60][61] It has been reported that the decreasing energy metabolism in the human body under various pathological conditions disturbs the metabolic pathways of the urea cycle resulting in the altered concentrations of urea and creatinine excretion in urine. [48] Creatinine end product of muscle metabolism is filtered by the kidneys from the blood and excreted in urine. [43] From Fig.…”

“…Because tryptophan metabolism is related with the immune response of the human body, any alterations in the tryptophan metabolism and the rate-limiting enzyme indoleamine 2,3-dioxygenase activity may lead to changes in the physiopathological conditions and act as a promoter in the progression of cancer and other disorders such as neuropsychiatric syndromes and other depressive disorder. [48,70,71] Earlier literature reports that indole -a metabolic intermediate of tryptophan -is an intoxicating co-carcinogen for the urinary bladder cancer in animal models. It is formed from the dietary tryptophan by tryptophanase of intestinal micro flora such as Escherichia coli.…”

GENOTOXICITY OF BENZALDEHYDE IN Drosophila melanogaster USING THE WING SOMATIC MUTATION AND RECOMBINATION TEST (SMART) AND PROTEIN PROFILING

“…These genotoxic substances include a variety of Copyright: Copyright©2012 Deepa P.V., et al This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited. chemical compounds [2]. In the living cell, DNA undergoes frequent chemical change, especially when it is replicated.…”

“…Mutagens are chemicals or physical factors (such as radiation) that increase the rate of mutation in the cells of bacteria, plants and animals (including humans) [3]. Chemicals able to induce genotoxic effects by mechanisms other than covalent binding are of special interest to scientist [2]. A great deal of work is being devoted to the validation of genotoxicity test procedures able to detect drugs that cause genetic damage by interaction with other cellular targets such as enzymes and microtubules particularly because they play a critical role in DNA replication or in the segregation of chromosomes during cell division [4].…”