Evidence map›Paper›PMID 33338921›Full record

ArticleRedox biology2021

Hexameric procyanidins inhibit colorectal cancer cell growth through both redox and non-redox regulation of the epidermal growth factor signaling pathway.

Elena Daveri, Ana M Adamo, Eugenia Alfine, Wei Zhu, Patricia I Oteiza

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Redox biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
2.1field-weighted citation impact, top 14% of its field
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

15 citing papers in PubMed, 28 citations in OpenAlex.

  1. Review
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  3. Procyanidin B2-induced LKB1-AMPK activation mitigates vascular smooth muscle cell proliferation through inhibition of mTOR signaling.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2025
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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

5 authors at 3 institutions in 3 countries.

Elena DaveriDepartments of Nutrition University of California, Davis, 95616, Davis, CA, USA; Departments of Environmental Toxicology, University of California, Davis, 95616, Davis, CA, USA; Unit of Immunotherapy of Human Tumors, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133, Milan, Italy.
Ana M AdamoDepartment of Biological Chemistry and IQUIFIB (UBA-CONICET), Facultad de Farmacia y Bioquímica, 1113, Universidad de Buenos Aires, Buenos Aires, Argentina.
Eugenia AlfineDepartments of Nutrition University of California, Davis, 95616, Davis, CA, USA; Departments of Environmental Toxicology, University of California, Davis, 95616, Davis, CA, USA.
Wei ZhuDepartments of Nutrition University of California, Davis, 95616, Davis, CA, USA; Departments of Environmental Toxicology, University of California, Davis, 95616, Davis, CA, USA.
Patricia I OteizaDepartments of Nutrition University of California, Davis, 95616, Davis, CA, USA; Departments of Environmental Toxicology, University of California, Davis, 95616, Davis, CA, USA. Electronic address: poteiza@ucdavis.edu.
University of California, Davis · USConsejo Nacional de Investigaciones Científicas y Técnicas · ARFondazione IRCCS Istituto Nazionale dei Tumori · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Dietary proanthocyanidins (PAC) consumption is associated with a decreased risk for colorectal cancer (CRC). Dysregulation of the epidermal growth factor (EGF) receptor (EGFR) signaling pathway is frequent in human cancers, including CRC. We previously showed that hexameric PAC (Hex) exert anti-proliferative and pro-apoptotic actions in human CRC cells. This work investigated if Hex could exert anti-CRC effects through its capacity to regulate the EGFR pathway. In proliferating Caco-2 cells, Hex acted attenuating EGF-induced EGFR dimerization and NADPH oxidase-dependent phosphorylation at Tyr 1068, decreasing EGFR location at lipid rafts, and inhibiting the downstream activation of pro-proliferative and anti-apoptotic pathways, i.e. Raf/MEK/ERK1/2 and PI3K/Akt. Hex also promoted EGFR internalization both in the absence and presence of EGF. While Hex decreased EGFR phosphorylation at Tyr 1068, it increased EGFR Tyr 1045 phosphorylation. The latter provides a docking site for the ubiquitin ligase c-Cbl and promotes EGFR degradation by lysosomes. Importantly, Hex acted synergistically with the EGFR-targeted chemotherapeutic drug Erlotinib, both in their capacity to decrease EGFR phosphorylation and inhibit cell growth. Thus, dietary PAC could exert anti-CRC actions by modulating, through both redox- and non-redox-regulated mechanisms, the EGFR pro-oncogenic signaling pathway. Additionally, Hex could also potentiate the actions of EGFR-targeted drugs.

Indexed as

Colorectal NeoplasmsProanthocyanidinsCaco-2 CellsCell Line, TumorEpidermal Growth FactorErbB ReceptorsHumansOxidation-ReductionPhosphatidylinositol 3-KinasesPhosphorylationSignal TransductionEGFR protein, humanEpidermal Growth FactorErbB ReceptorsPhosphatidylinositol 3-KinasesProanthocyanidinsColorectal cancerEpidermal growth factor receptorNADPH oxidaseProanthocyanidinsRedox regulation

Identifiers

PMID33338921
PMCPMC7750420
OpenAlexW3111343048

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.