Evidence mapPaperPMID 41330216Full record

ArticleRedox biology2025

TRPA1 activation prompts lysosome-mediated Nrf2 degradation enhancing the killing of colorectal cancer cells.

Najmeh Eskandari, Davide Delisi, Maedeh Vakili Saatloo, Gizem Keceli, Nathalia Pinheiro, Scott Eblen, Nazareno Paolocci, Saverio Gentile

Abstract read
In one paragraph

Article in Redox biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Compartmental pH regulation in cancer and antitumor immunity: therapeutic opportunities and challenges.Apoptosis : an international journal on programmed cell death · 2026
    Review
  2. Review
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

8 authors.

Najmeh EskandariDepartment of Biochemistry and Cell Biology, Medical University of South Carolina, United States.
Davide DelisiDepartment of Biochemistry and Cell Biology, Medical University of South Carolina, United States.
Maedeh Vakili SaatlooDepartment of Biochemistry and Cell Biology, Medical University of South Carolina, United States; Department of Periodontology, Henry M. Goldman School of Dental Medicine, Boston University, MA, United States.
Gizem KeceliDivision of Cardiology, Department of Medicine, Johns Hopkins University, United States.
Nathalia PinheiroDepartment of Biochemistry and Cell Biology, Medical University of South Carolina, United States.
Scott EblenDepartment of Pharmacology and Immunology, Medical University of South Carolina, United States.
Nazareno PaolocciDivision of Cardiology, Department of Medicine, Johns Hopkins University, United States; Dipartimento di Scienze Biomediche, Universita' di Padova, United States.
Saverio GentileDepartment of Biochemistry and Cell Biology, Medical University of South Carolina, United States. Electronic address: gentilsa@musc.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Redox homeostasis is crucial for cancer cell survival and resistance to therapy. The transcription factor NRF2, a master regulator of antioxidant and metabolic genes, is often upregulated in tumors to mitigate oxidative stress. Although NRF2 stability is canonically governed by KEAP1-CUL3-proteasome degradation, emerging evidence implicates lysosomal and autophagic pathways in non-canonical NRF2 turnover. The mechanisms by which these alternative pathways are engaged during chronic oxidative signaling remain unclear. We investigated whether sustained activation of the redox-sensitive ion channel TRPA1 by cannabidiol (CBD) disrupts redox homeostasis and promotes NRF2 degradation in colorectal cancer models. Using five independent CRC cell lines (RKO, HCT116, HT29, SW480, and MC38), we assessed reactive oxygen species (ROS), mitochondrial function, autophagy, and NRF2 protein dynamics through biochemical assays, lysosomal fractionation, and imaging. Xenograft models were used for in vivo validation. Chronic TRPA1 activation induced a biphasic ROS response, characterized by an early increase linked to mitochondrial Ca

Indexed as

Colorectal NeoplasmsLysosomesNF-E2-Related Factor 2TRPA1 Cation ChannelAnimalsAutophagyCell Line, TumorHumansMiceMitochondriaOxidation-ReductionOxidative StressProteolysisReactive Oxygen SpeciesXenograft Model Antitumor AssaysNFE2L2 protein, humanNF-E2-Related Factor 2Reactive Oxygen SpeciesTRPA1 Cation ChannelTRPA1 protein, human

Identifiers

PMID41330216
PMCPMC12719038

What Socratic holds

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LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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 Socratic graph.