Evidence map›Paper›PMID 42802274›Full record

ArticleNature communications2026

Triptolide sensitizes cancer cells to nucleoside DNA methyltransferase inhibitors through inhibition of DCTPP1-mediated cell-intrinsic resistance.

Jianyong Liu, Qing-Li He, Jianya Zhou, Ajay M Vaghasia, Roshan Chikarmane, Glenn Hauk, Archana Rachakonda, Nicole Castagna, Ruchama C Steinberg, Minh-Tam Pham and 25 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

35 authors.

Jianyong LiuThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA.
Qing-Li HeDepartment of Pharmacology and Molecular Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Jianya ZhouDepartment of Respiratory Disease, Thoracic Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, P. R. China.
Ajay M VaghasiaThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA.
Roshan ChikarmaneThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA.ORCID 0000-0002-7784-6085
Glenn HaukInstitute for Basic Biomedical Sciences and Department of Biophysics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Archana RachakondaThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA.
Nicole CastagnaThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA.
Ruchama C SteinbergThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA.ORCID 0000-0003-2897-7561
Minh-Tam PhamThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA.
Jordan M GreggThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA.ORCID 0000-0002-2024-8586
Alok MishraThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA.
Yuhan YangThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA.ORCID 0009-0008-0722-7407
Talha AnwarThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA.
Roy EliasThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA.
Pengshan LiThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA.
Jasmine Yun-Tong KungThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA.ORCID 0009-0001-2766-5817
Anthony C O'DonnellInstitute for Basic Biomedical Sciences and Department of Biophysics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Nicole M AndersThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA.
Teresia M WanjikuThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA.
Philipp NuhnThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA.
Joong Sup ShimFaculty of Health Sciences, University of Macau, Taipa, Macau SAR.ORCID 0000-0003-0167-7307
Hugh GiovinazzoThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA.
David M EsopiThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA.
Kunhwa KimThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA.
Jonathan CoulterThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA.
Rulin WangThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA.ORCID 0000-0002-6177-1058
Jianying ZhouDepartment of Respiratory Disease, Thoracic Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, P. R. China.
Michelle A RudekThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA.
Kathleen GabrielsonDepartment of Molecular and Comparative Pathobiology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Angelo M De MarzoThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA.ORCID 0000-0003-4847-5307
James M BergerThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA.ORCID 0000-0003-0666-1240
Jun O LiuThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA.ORCID 0000-0003-3842-9841
William G NelsonThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA. bnelson@jhmi.edu.ORCID 0000-0002-4379-0730
Srinivasan YegnasubramanianThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA. syegnasu@jhmi.edu.ORCID 0000-0003-0744-6606

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI ALAN KEITH MEEKER · 1985 to 2026
$208.6M
QAQC Johns Hopkins Institute for Clinical and Translational ResearchUL1TR003098 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2019 to 2023
$57.7M
TRANSGENIC MODELS FOR PROSTATE CANCER AND AUTOIMMUNITYP50CA058236 · NCI · JOHNS HOPKINS UNIVERSITY · PI NELSON, WILLIAM GEORGE · 1992 to 2020
$43.9M
GSTPI PROMOTOR HYPERMETHYLATION IN HUMAN PROSTATE CANCERR01CA070196 · NCI · JOHNS HOPKINS UNIVERSITY · PI NELSON, WILLIAM GEORGE · 1996 to 2012
$3.9M
Role of TOP2B in generating complex genomic rearrangements in human cancerR01CA183965 · NCI · JOHNS HOPKINS UNIVERSITY · PI WHEELAN, SARAH J, YEGNASUBRAMANIAN, SRINIVASAN · 2014 to 2018
$1.7M
UPLC with Tandem MS for Sensitive Quantitative Analysis of Small MoleculesS10RR026824 · NCRR · JOHNS HOPKINS UNIVERSITY · PI RUDEK, MICHELLE A · 2010 to 2010
$429k
Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) P50CA058236, R01CA183965, R01CA070196, P30CA006973, S10RR026824, UL1TR003098NCATS NIH HHS UL1 TR003098NCI NIH HHS P30 CA006973NCI NIH HHS P50 CA058236NCI NIH HHS R01 CA070196NCI NIH HHS R01 CA183965NCRR NIH HHS S10 RR026824Prostate Cancer Foundation (PCF) Challenge Awards
6 · The paper itself

Abstract

Abnormal DNA hypermethylation mediated by DNA methyltransferases (DNMT) is a nearly universal hallmark of human cancers. However, while DNA methyltransferase inhibitors (DNMTi) such as decitabine and azacitidine are effective in treating myelodysplatic syndrome/leukemia, they have had limited utility for the majority of other cancers. Through a chemical library screen, we identify that triptolide, a diterpenoid epoxide from Tripterygium wilfordii, and multiple of its analogs, significantly augment the epigenetic and anti-cancer effects of decitabine in vitro and in vivo. These effects are attributable to inhibition of DCTPP1-mediated cleavage of 5-aza-deoxycytidine triphosphate, the convergent activated metabolite of nucleoside DNMTi, leading to enhanced drug incorporation into genomic DNA, increased DNMT degradation, enhanced DNA demethylation and associated transcriptional reprogramming. We show that high DCTPP1 expression mediates cell-intrinsic resistance to nucleoside DNMTi, and that triptolide and its analogs could overcome this resistance. These findings nominate combining DNMTi with triptolide or its analogs as a rational cancer therapeutic strategy.

Indexed as

DiterpenesDrug Resistance, NeoplasmEnzyme InhibitorsPhenanthrenesAnimalsAzacitidineCell Line, TumorDecitabineDNA MethylationEpoxy CompoundsHumansMiceAzacitidineDecitabineDiterpenesEnzyme InhibitorsEpoxy CompoundsPhenanthrenestriptolide

Identifiers

PMID42802274
PMCPMC13616921

What OpenQuestion holds

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Registered trials

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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.