Rapid distribution of tryptophol (3-indole ethanol) to the brain and other tissues.

Cornford, Eain M.; Bocash, William D.; Braun, Leon D.; Crane, Paul D.; Oldendorf, William H.; MacInnis, A. J.

doi:10.1172/jci109419

Cited by 35 publications

(21 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Disulfiram (DSF) is used to treat alcoholism based on its inhibitory effect on acetaldehyde dehydrogenases, which are encoded by 3 of the 19 different aldehyde dehydrogenase (ALDH) genes, ALDH1A1, ALDH2, and ALDH1B1/ALDH5. It has mild side effects in humans that include headache, metallic taste, and drowsiness due to increased production of tryptophol in the liver 14 , 15 . Beyond treatment of alcoholism, disulfiram was found in non-biased drug screens to show anti-neoplastic activity against prostate cancer and glioblastoma 16 - 18 and is the subject of ongoing clinical trials for lung and liver cancer 19 , 20 .…”

Section: Resultsmentioning

confidence: 99%

High-throughput screen identifies disulfiram as a potential therapeutic for triple-negative breast cancer cells: Interaction with IQ motif-containing factors

et al. 2013

View full text Add to dashboard Cite

Triple-negative breast cancer (TNBC) represents an aggressive subtype, for which radiation and chemotherapy are the only options. Here we describe the identification of disulfiram, an FDA-approved drug used to treat alcoholism, as well as the related compound thiram, as the most potent growth inhibitors following high-throughput screens of 3185 compounds against multiple TNBC cell lines. The average IC50 for disulfiram was ~300 nM. Drug affinity responsive target stability (DARTS) analysis identified IQ motif-containing factors IQGAP1 and MYH9 as direct binding targets of disulfiram. Indeed, knockdown of these factors reduced, though did not completely abolish, cell growth. Combination treatment with 4 different drugs commonly used to treat TNBC revealed that disulfiram synergizes most effectively with doxorubicin to inhibit cell growth of TNBC cells. Disulfiram and doxorubicin cooperated to induce cell death as well as cellular senescence, and targeted the ESA+/CD24-/low/CD44+ cancer stem cell population. Our results suggest that disulfiram may be repurposed to treat TNBC in combination with doxorubicin.

show abstract

Section: Resultsmentioning

confidence: 99%

High-throughput screen identifies disulfiram as a potential therapeutic for triple-negative breast cancer cells: Interaction with IQ motif-containing factors

et al. 2013

View full text Add to dashboard Cite

show abstract

“…The finding on high susceptibility of HepG2 cells to tryptophol deserves particular attention because of many interactions between tryptophan and alcohol in mammalian liver (39), including its metabolism into tryptophol. In addition, tryptophol is known formed in the liver after treatment with disulfi ram (40).…”

Section: Discussionmentioning

confidence: 99%

Assessment of Tryptophol Genotoxicity in Four Cell Lines In Vitro: A Pilot Study with Alkaline Comet Assay

Kosalec¹,

Ramić²,

Jelić³

et al. 2011

Archives of Industrial Hygiene and Toxicology

View full text Add to dashboard Cite

Tryptophol is an aromatic alcohol and secondary metabolite of the opportunistic fungus Candida albicans. Although its toxicity profi le at cell level has been poorly investigated, recent data point to cytotoxic, cytostatic, and genotoxic effects in lymphocytes and the induction of apoptosis in leukaemic blood monocytes. In this pilot study we evaluated the genotoxicity of tryptophol in vitro on four permanent cell lines of animal and human origin: ovary cells, alveolar epithelium, liver cells, and blood monocytes using the alkaline comet assay. We selected cells that might be principal targets of tryptophol and other low-molecular geno(toxins) secreted by Candida albicans during host invasion. Our results suggest that tryptophol applied in vitro at 2 mmol L -1 for 24 h damages DNA in HepG2, A549 and THP-1 cells, obviously due to bioactivation and/or decomposition of the parent compound, which results in the formation of more genotoxic compound(s) and production of reactive species that additionally damage DNA. On the other hand, notably lower levels of primary DNA damage were recorded in CHO cells, which lack metabolic activity. Future studies with tryptophol should look further into mechanisms involved in its toxic action and should focus on other cell types prone to infection with Candida spp. such as vaginal epithelial cells or keratinocytes of human origin.

show abstract

“…Tryptophol present in wine and beer as byproducts of fermentation can also be produced in the human liver after disulfiram treatment for chronic alcoholism [8]. The synthesis of tryptophol by yeast was first described by Felix Ehrlich in 1912 [9] as the metabolic conversion of amino acids via the successive steps of transamination, decarboxylation, and reduction [10].…”

Section: Introductionmentioning

confidence: 99%

Enhancing the Yields of Phenolic Compounds during Fermentation Using <i>Saccharomyces cerevisiae</i> Strain 96581

Banach¹,

Ooi²

2014

FNS

View full text Add to dashboard Cite

Phenylethanol, tyrosol, and tryptophol are phenolic compounds or fusel alcohols formed via the Ehrlich pathway by yeast metabolism. These compounds can yield health benefits as well as contribute to the flavors and aromas of fermented food and beverages. This research shows that Saccharomyces cerevisiae Strain 96581 is capable of producing significantly higher levels of these three compounds when the precursor amino acids were supplemented into either the Chardonnay concentrate for wine-making or the malt concentrate for brewing English Ale. Strain 96581 can produce phenylethanol, tyrosol, and tryptophol as high as 434 mg/kg, 365 mg/kg, and 129 mg/kg, respectively, in the beer fermentation. The performance of Ale yeast WLP002 from White Labs Inc. was also analyzed for comparison. Strain 96581 outperformed WLP002 in the control beer, the amino acids supplemented beer, and the kiwi-beer background. This shows that Strain 96581 is more effective than WLP002 in converting the malt and the kiwi fruit supplements via its endogenous enzymes.

show abstract

Rapid distribution of tryptophol (3-indole ethanol) to the brain and other tissues.

Cited by 35 publications

References 39 publications

High-throughput screen identifies disulfiram as a potential therapeutic for triple-negative breast cancer cells: Interaction with IQ motif-containing factors

High-throughput screen identifies disulfiram as a potential therapeutic for triple-negative breast cancer cells: Interaction with IQ motif-containing factors

Assessment of Tryptophol Genotoxicity in Four Cell Lines In Vitro: A Pilot Study with Alkaline Comet Assay

Enhancing the Yields of Phenolic Compounds during Fermentation Using <i>Saccharomyces cerevisiae</i> Strain 96581

Contact Info

Product

Resources

About

Rapid distribution of tryptophol (3-indole ethanol) to the brain and other tissues.

Cited by 35 publications

References 39 publications

High-throughput screen identifies disulfiram as a potential therapeutic for triple-negative breast cancer cells: Interaction with IQ motif-containing factors

High-throughput screen identifies disulfiram as a potential therapeutic for triple-negative breast cancer cells: Interaction with IQ motif-containing factors

Assessment of Tryptophol Genotoxicity in Four Cell Lines In Vitro: A Pilot Study with Alkaline Comet Assay

Enhancing the Yields of Phenolic Compounds during Fermentation Using &lt;i&gt;Saccharomyces cerevisiae&lt;/i&gt; Strain 96581

Contact Info

Product

Resources

About

Enhancing the Yields of Phenolic Compounds during Fermentation Using <i>Saccharomyces cerevisiae</i> Strain 96581