ArticlePloS one2013
UDP-glucuronosyltransferase 1A compromises intracellular accumulation and anti-cancer effect of tanshinone IIA in human colon cancer cells.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 2 of them syntheses that pooled it.
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
14 citing papers in PubMed, 2 syntheses or guidelines pooled it, 33 citations in OpenAlex.
- Unveiling the Anticancer Potential of Urolithin A in Colorectal Cancer: A Systematic Review.Oncology research · 2026Pooled it
- Roles of Reactive Oxygen Species in Anticancer Therapy with Salvia miltiorrhiza Bunge.Oxidative medicine and cellular longevity · 2016Pooled it
- Pharmacokinetics and tolerability of MB12066, a beta-lapachone derivative targeting NAD(P)H: quinone oxidoreductase 1: two independent, double-blind, placebo-controlled, combined single and multiple ascending dose first-in-human clinical trials.Drug design, development and therapy · 2017Trial
- Improved Lipophilicity Is Associated with the Cytotoxic Activity of Chlorogenic Acid Esters in In Vitro Colorectal Cancer Models.Molecules (Basel, Switzerland) · 2026Article
- Prokaryotic Molecular Defense Mechanisms and Their Potential Applications in Cancer Biology: A Special Consideration for Cyanobacterial Systems.Current issues in molecular biology · 2026Review
- In Vitro and In Silico Study on the Impact of Chlorogenic Acid in Colorectal Cancer Cells: Proliferation, Apoptosis, and Interaction with β-Catenin and LRP6.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Modulatory Effect of Chlorogenic Acid and Coffee Extracts on Wnt/β-Catenin Pathway in Colorectal Cancer Cells.Nutrients · 2022Article
- Identification and validation of xenobiotic metabolism-associated prognostic signature based on five genes to evaluate immune microenvironment in colon cancer.Journal of gastrointestinal oncology · 2021Article
- Sulforaphane suppresses carcinogenesis of colorectal cancer through the ERK/Nrf2‑UDP glucuronosyltransferase 1A metabolic axis activation.Oncology reports · 2020Article
- Expression Patterns of Xenobiotic-Metabolizing Enzymes in Tumor and Adjacent Normal Mucosa Tissues among Patients with Colorectal Cancer: The ColoCare Study.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2020Observational
- Tanshinone IIA Attenuates Insulin Like Growth Factor 1 -Induced Cell Proliferation in PC12 Cells through the PI3K/Akt and MEK/ERK Pathways.International journal of molecular sciences · 2018Article
- De-novo NAD+ synthesis regulates SIRT1-FOXO1 apoptotic pathway in response to NQO1 substrates in lung cancer cells.Oncotarget · 2016Article
- Article
- UDP glucuronosyltransferase 1A expression levels determine the response of colorectal cancer cells to the heat shock protein 90 inhibitor ganetespib.Cell death & disease · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeNAD(P)H: quinone oxidoreductase 1 (NQO1) mediated quinone reduction and subsequent UDP-glucuronosyltransferases (UGTs) catalyzed glucuronidation is the dominant metabolic pathway of tanshinone IIA (TSA), a promising anti-cancer agent. UGTs are positively expressed in various tumor tissues and play an important role in the metabolic elimination of TSA. This study aims to explore the role of UGT1A in determining the intracellular accumulation and the resultant apoptotic effect of TSA. EXPERIMENTAL APPROACH: We examined TSA intracellular accumulation and glucuronidation in HT29 (UGT1A positive) and HCT116 (UGT1A negative) human colon cancer cell lines. We also examined TSA-mediated reactive oxygen species (ROS) production, cytotoxicity and apoptotic effect in HT29 and HCT116 cells to investigate whether UGT1A levels are directly associated with TSA anti-cancer effect. UGT1A siRNA or propofol, a UGT1A9 competitive inhibitor, was used to inhibit UGT1A expression or UGT1A9 activity. KEY
resultsMultiple UGT1A isoforms are positively expressed in HT29 but not in HCT116 cells. Cellular S9 fractions prepared from HT29 cells exhibit strong glucuronidation activity towards TSA, which can be inhibited by propofol or UGT1A siRNA interference. TSA intracellular accumulation in HT29 cells is much lower than that in HCT116 cells, which correlates with high expression levels of UGT1A in HT29 cells. Consistently, TSA induces less intracellular ROS, cytotoxicity, and apoptotic effect in HT29 cells than those in HCT116 cells. Pretreatment of HT29 cells with UGT1A siRNA or propofol can decrease TSA glucuronidation and simultaneously improve its intracellular accumulation, as well as enhance TSA anti-cancer effect. CONCLUSIONS AND IMPLICATIONS: UGT1A can compromise TSA cytotoxicity via reducing its intracellular exposure and switching the NQO1-triggered redox cycle to metabolic elimination. Our study may shed a light in understanding the cellular pharmacokinetic and molecular mechanism by which UGTs determine the chemotherapy effects of drugs that are UGTs' substrates.
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.