ArticleCarcinogenesis2014
Dihydromethysticin from kava blocks tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung tumorigenesis and differentially reduces DNA damage in A/J mice.
Article in Carcinogenesis, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 41 citations in OpenAlex.
- AB-Free Kava and Dihydromethysticin Inhibit Chronic Hexavalent Chromium Exposure-Induced Cell Malignant Transformation through Down-Regulating RNA Splicing Factor SNRPA1 Expression.Chemical research in toxicology · 2026Article
- Flavokavains A- and B-Free Kava Enhances Resilience against the Adverse Health Effects of Tobacco Smoke in Mice.ACS pharmacology & translational science · 2024Article
- Opportunities and Challenges of Kava in Lung Cancer Prevention.International journal of molecular sciences · 2023Review
- Kavalactone Kawain Impedes Urothelial Tumorigenesis in UPII-Mutant Ha-Ras Mice via Inhibition of mTOR Signaling and Alteration of Cancer Metabolism.Molecules (Basel, Switzerland) · 2023Article
- Dietary Phytochemicals as Potential Chemopreventive Agents against Tobacco-Induced Lung Carcinogenesis.Nutrients · 2023Review
- The medicinal mushroomFrontiers in pharmacology · 2023Article
- Clinical pharmacokinetics of kavalactones after oral dosing of standardized kava extract in healthy volunteers.Journal of ethnopharmacology · 2022Article
- Suppressing the activation of protein kinase A as a DNA damage-independent mechanistic lead for dihydromethysticin prophylaxis of NNK-induced lung carcinogenesis.Carcinogenesis · 2022Article
- An Updated Review on the Psychoactive, Toxic and Anticancer Properties of Kava.Journal of clinical medicine · 2022Review
- In vitro inhibition of carboxylesterase 1 by Kava (Piper methysticum) Kavalactones.Chemico-biological interactions · 2022Article
- Article
- Characterization of adductomic totality of NNK, (R)-NNAL and (S)-NNAL in A/J mice, and their correlations with distinct lung carcinogenicity.Carcinogenesis · 2022Article
- Kava as a Clinical Nutrient: Promises and Challenges.Nutrients · 2020Review
- Oral Dosing of Dihydromethysticin Ahead of Tobacco Carcinogen NNK Effectively Prevents Lung Tumorigenesis in A/J Mice.Chemical research in toxicology · 2020Article
- The Impact of One-week Dietary Supplementation with Kava on Biomarkers of Tobacco Use and Nitrosamine-based Carcinogenesis Risk among Active Smokers.Cancer prevention research (Philadelphia, Pa.) · 2020Article
- Flaxseed Consumption Inhibits Chemically Induced Lung Tumorigenesis and Modulates Expression of Phase II Enzymes and Inflammatory Cytokines in A/J Mice.Cancer prevention research (Philadelphia, Pa.) · 2018Article
- A stable isotope dilution tandem mass spectrometry method of major kavalactones and its applications.PloS one · 2018Article
- Pilot in Vivo Structure-Activity Relationship of Dihydromethysticin in Blocking 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone-Induced OJournal of medicinal chemistry · 2017Article
- Kavalactone yangonin induces autophagy and sensitizes bladder cancer cells to flavokawain A and docetaxel via inhibition of the mTOR pathway.Journal of biomedical research · 2017Article
- Context Matters: Contribution of Specific DNA Adducts to the Genotoxic Properties of the Tobacco-Specific Nitrosamine NNK.Chemical research in toxicology · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
We have previously shown that kava and its flavokavain-free Fraction B completely blocked 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis in A/J mice with a preferential reduction in NNK-induced O (6)-methylguanine (O (6)-mG). In this study, we first identified natural (+)-dihydromethysticin (DHM) as a lead compound through evaluating the in vivo efficacy of five major compounds in Fraction B on reducing O (6)-mG in lung tissues. (+)-DHM demonstrated outstanding chemopreventive activity against NNK-induced lung tumorigenesis in A/J mice with 97% reduction of adenoma multiplicity at a dose of 0.05mg/g of diet (50 ppm). Synthetic (±)-DHM was equally effective as the natural (+)-DHM in these bioassays while a structurally similar analog, (+)-dihydrokavain (DHK), was completely inactive, revealing a sharp in vivo structure-activity relationship. Analyses of an expanded panel of NNK-induced DNA adducts revealed that DHM reduced a subset of DNA adducts in lung tissues derived from 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL, the active metabolite of NNK). Preliminary 17-week safety studies of DHM in A/J mice at a dose of 0.5mg/g of diet (at least 10× its minimum effective dose) revealed no adverse effects, suggesting that DHM is likely free of kava's hepatotoxic risk. These results demonstrate the outstanding efficacy and promising safety margin of DHM in preventing NNK-induced lung tumorigenesis in A/J mice, with a unique mechanism of action and high target specificity.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.