Tryptophan and carcinogenesis: Review and update on how tryptophan may act

Sidransky, Herschel

doi:10.1080/01635589709514623

Cited by 15 publications

(18 citation statements)

References 82 publications

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“…Although some of the enzymes may play a role in detoxifying chemical carcinogens, others may activate them into ultimate carcinogens. It is possible that, in some individuals, the balance may become tilted toward greater level of ultimate carcinogens, which induced cancer [Sidransky, 1997]. Rodents seem to be more likely to have liver cancer than dogs and humans.…”

Section: Tryptophan Metabolites and Bladder Cancermentioning

confidence: 97%

“…There were reports that tryptophan has antioxidant activities [Christen et al, 1990]. Such effects may play a role in relation to tryptophan and its preventive effect in carcinogenesis under certain conditions [Sidransky, 1997]. However, the exact mechanisms involved are not clear.…”

Section: Tryptophan As An Inhibitory Agent Of Chemical Carcinogenesismentioning

confidence: 98%

“…[Chung et al, 1975a]. It was reported that about 3% of tryptophan is converted to IAA in the gastrointestinal tract [Sidransky, 1997]. The formation of IAA proceeds through the intermediate indole pyruvic acid via transamination with a-ketoglutarate [Chung et al, 1975b].…”

Section: The Indole Pathwaymentioning

confidence: 99%

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Possible roles of excess tryptophan metabolites in cancer

Chung

Gadupudi

2011

Environ and Mol Mutagen

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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.

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Section: Tryptophan Metabolites and Bladder Cancermentioning

confidence: 97%

Section: Tryptophan As An Inhibitory Agent Of Chemical Carcinogenesismentioning

confidence: 98%

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Possible roles of excess tryptophan metabolites in cancer

Chung

Gadupudi

2011

Environ and Mol Mutagen

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“…The best-publicized risk was the 1989 epidemic of eosinophilia-myalgia linked to tryptophan use. However, this association was more likely due to impurities rather than to the tryptophan itself (Sidransky, 1997;Williamson, Tomlinson, Mishra, Gleich, & Naylor, 1998), and it may have partly resulted from circular diagnostic practice (Blackburn, 1997;Wagner, Elmore, & Horwitz, 1996). In sum, amino acid supplementation does not appear a promising area to explore further, though protein-rich diets might be explored as a specific correction of the reported nitrogen-wasting metabolic aberrations or as palliation of alleged hypoglycemia.…”

Section: Amino Acid Supplementationmentioning

confidence: 99%

“…However, no lasting benefit beyond 2-3 months has been demonstrated since tolerance usually develops (Wood, Reimherr, & Wender, 1985b), and even short-term benefit was not found in some studies (Eisenberg, Asnis, van Praag, & Vela, 1988;Ghose, 1983;Zametkin, Karoum, & Rapoport, 1987). Further, such supplementation, while originally considered benign, may carry some risk (Pakes, 1978;Sidransky, 1997;Sternberg, 1996). The best-publicized risk was the 1989 epidemic of eosinophilia-myalgia linked to tryptophan use.…”

Section: Amino Acid Supplementationmentioning

confidence: 99%

Treatment alternatives for Attention-Deficit! Hyperactivity Disorder (ADHD)

Arnold

1999

J Atten Disord

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Results:Twenty-three alternate Tx were identified, ranging in scientific documentation from discrediting controlled studies through mere hypotheses to positive controlled double-blind clinical trials. Many of them are applicable only to a restricted etiological subgroup. The oligoantigenic or few-foods diet has convincing double-blind evidence of efficacy in multiple trials for a properly selected subgroup. Enzyme-potentiated desensitization to foods, relaxation/EMG biofeedback, and deleading also have controlled evidence of efficacy. Glyconutritional supplementation, iron supplementation, magnesium supplementation, Chinese herbals, EEG biofeedback, meditation, mirror feedback, channel-specific perceptual training, and vestibular stimulation all have promising prospective pilot data. Single-vitamin megadosage has some intriguing pilot trial data. Zinc supplementation is hypothetically supported by systematic case-control data but has no systematic clinical trial. Laser acupuncture has promising unpublished pilot data. Essential fatty acid supplementation has promising systematic case-control data but clinical trials are equivocal. Recommended-Daily-Allowance vitamin supplementation, nonChinese herbals, homeopathic remedies, and antifungal therapy have no systematic data in ADHD. Megadose multivitamin combinations are probably ineffective for most patients and possibly dangerous. Simple sugar restriction and hypnosis seem ineffective. Amino acid supplementation, though mildly effective in the short term, is not effective beyond a few weeks. Thyroid Tx is effective in the presence of documented thyroid abnormality, but not otherwise. ConclusionSome alternate Tx of ADHD are effective or probably effective, but mainly for restricted etiologic subgroups. In some cases they are the Tx of choice, and initial evaluation should consider the relevant etiologies. A few have failed to prove effective in controlled trials. Most need research to determine whether they are effective and/or to define the applicable subgroup. Some of them, though not safer than standard Tx, may be preferable for an etiologic subgroup.

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Biomarkers in bladder cancer: A metabolomic approach using in vitro and ex vivo model systems

Rodrigues

Jerónimo

Henrique

et al. 2016

Intl Journal of Cancer

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Metabolomics has recently proved to be useful in the area of biomarker discovery for cancers in which early diagnostic and prognostic biomarkers are urgently needed, as is the case of bladder cancer (BC). This article presents a comprehensive review of the literature on the metabolomic studies on BC, highlighting metabolic pathways perturbed in this disease and the altered metabolites as potential biomarkers for BC detection. Current disease model systems used in the study of BC metabolome include in vitro-cultured cancer cells, ex vivo neoplastic bladder tissues and biological fluids, mainly urine but also blood serum/plasma, from BC patients. The major advantages and drawbacks of each model system are discussed. Based on available data, it seems that BC metabolic signature is mainly characterized by alterations in metabolites related to energy metabolic pathways, particularly glycolysis, amino acid and fatty acid metabolism, known to be crucial for cell proliferation, as well as glutathione metabolism, known to be determinant in maintaining cellular redox balance. In addition, purine and pyrimidine metabolism as well as carnitine species were found to be altered in BC. Finally, it is emphasized that, despite the progress made in respect to novel biomarkers for BC diagnosis, there are still some challenges and limitations that should be addressed in future metabolomic studies to ensure their translatability to clinical practice. Bladder Cancer and the Need for Novel Diagnosis StrategiesBladder cancer (BC) is the second most common human malignancy affecting the urinary system and one of the most deadly cancers worldwide. 1 Its incidence continues to rise and mortality rates have remained unchanged over the past 3 decades, since successful treatments depend mainly on early detection. 2 Risk factors are associated with environmental, dietary/lifestyle, especially smoking and genetic factors. 3,4 BC is a heterogeneous and multifocal malignancy, being divided in 3 main histological subtypes. Most BCs are transitional cell carcinomas (TCC) (90%), 5 also called urothelial cell carcinomas since they develop from the cells of the bladder lining (urothelium). The other two types, squamous cell carcinoma and adenocarcinomas, represent 10% of BC. 5 Noteworthy, metabolomic studies on BC are, however, mostly focused on urothelial bladder carcinoma. BC can be classified as low-grade or high-grade, depending on the degree by which cancer cells histologically differ from normal bladder cells, being high-grade BC more aggressive and invasive than low-grade. 6 Furthermore, BC is also classified as superficial or nonmuscle invasive bladder cancer (NMIBC) and invasive or muscle invasive bladder cancer (MIBC), based on the level of invasion of the muscular bladder wall. 6 Whereas NMIBC is restricted to the lining of the bladder, MIBC spreads and invades the muscle wall and other tissues/organs, and might also cause metastatic spread. 6,7 Remarkably, these two tumor types display quite distinct molecular characteristics. Indeed, NMI...

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Tryptophan and carcinogenesis: Review and update on how tryptophan may act

Cited by 15 publications

References 82 publications

Possible roles of excess tryptophan metabolites in cancer

Possible roles of excess tryptophan metabolites in cancer

Treatment alternatives for Attention-Deficit! Hyperactivity Disorder (ADHD)

Biomarkers in bladder cancer: A metabolomic approach using in vitro and ex vivo model systems

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