Evidence map›Paper›PMID 25338671›Full record

ArticleMolecular pharmacology2015

S-Adenosylmethionine and methylthioadenosine inhibit β-catenin signaling by multiple mechanisms in liver and colon cancer.

Tony W H Li, Hui Peng, Heping Yang, Steven Kurniawidjaja, Parizad Panthaki, Yuhua Zheng, José M Mato, Shelly C Lu

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

Article in Molecular pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
0.6field-weighted citation impact, top 32% 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

17 citing papers in PubMed, 27 citations in OpenAlex.

  1. Trial
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  6. Article
  7. Review
  8. The Crucial Roles of Intermediate Metabolites in Cancer.Cancer management and research · 2021
    Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. Review
  14. Article
  15. Review
  16. Article
  17. Inhibitory effect ofChinese medicine · 2016
    Article
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 at 4 institutions in 2 countries.

Tony W H LiDivision of Gastroenterology, Cedars Sinai Medical Center, Los Angeles, California (T.W.H.L., H.P., H.Y., S.C.L.); University of Southern California Research Center for Liver Diseases, Keck School of Medicine, Los Angeles, California (T.W.H.L., H.P., H.Y., S.K., P.P., S.C.L.); Department of Pediatric Gastroenterology, Hepatology, and Nutrition, Children's Hospital Los Angeles, Los Angeles, California (Y.Z.); and CIC bioGUNE, Ciberehd, Bizkaia, Spain (J.M.M.).
Hui PengDivision of Gastroenterology, Cedars Sinai Medical Center, Los Angeles, California (T.W.H.L., H.P., H.Y., S.C.L.); University of Southern California Research Center for Liver Diseases, Keck School of Medicine, Los Angeles, California (T.W.H.L., H.P., H.Y., S.K., P.P., S.C.L.); Department of Pediatric Gastroenterology, Hepatology, and Nutrition, Children's Hospital Los Angeles, Los Angeles, California (Y.Z.); and CIC bioGUNE, Ciberehd, Bizkaia, Spain (J.M.M.).
Heping YangDivision of Gastroenterology, Cedars Sinai Medical Center, Los Angeles, California (T.W.H.L., H.P., H.Y., S.C.L.); University of Southern California Research Center for Liver Diseases, Keck School of Medicine, Los Angeles, California (T.W.H.L., H.P., H.Y., S.K., P.P., S.C.L.); Department of Pediatric Gastroenterology, Hepatology, and Nutrition, Children's Hospital Los Angeles, Los Angeles, California (Y.Z.); and CIC bioGUNE, Ciberehd, Bizkaia, Spain (J.M.M.).
Steven KurniawidjajaDivision of Gastroenterology, Cedars Sinai Medical Center, Los Angeles, California (T.W.H.L., H.P., H.Y., S.C.L.); University of Southern California Research Center for Liver Diseases, Keck School of Medicine, Los Angeles, California (T.W.H.L., H.P., H.Y., S.K., P.P., S.C.L.); Department of Pediatric Gastroenterology, Hepatology, and Nutrition, Children's Hospital Los Angeles, Los Angeles, California (Y.Z.); and CIC bioGUNE, Ciberehd, Bizkaia, Spain (J.M.M.).
Parizad PanthakiDivision of Gastroenterology, Cedars Sinai Medical Center, Los Angeles, California (T.W.H.L., H.P., H.Y., S.C.L.); University of Southern California Research Center for Liver Diseases, Keck School of Medicine, Los Angeles, California (T.W.H.L., H.P., H.Y., S.K., P.P., S.C.L.); Department of Pediatric Gastroenterology, Hepatology, and Nutrition, Children's Hospital Los Angeles, Los Angeles, California (Y.Z.); and CIC bioGUNE, Ciberehd, Bizkaia, Spain (J.M.M.).
Yuhua ZhengDivision of Gastroenterology, Cedars Sinai Medical Center, Los Angeles, California (T.W.H.L., H.P., H.Y., S.C.L.); University of Southern California Research Center for Liver Diseases, Keck School of Medicine, Los Angeles, California (T.W.H.L., H.P., H.Y., S.K., P.P., S.C.L.); Department of Pediatric Gastroenterology, Hepatology, and Nutrition, Children's Hospital Los Angeles, Los Angeles, California (Y.Z.); and CIC bioGUNE, Ciberehd, Bizkaia, Spain (J.M.M.).
José M MatoDivision of Gastroenterology, Cedars Sinai Medical Center, Los Angeles, California (T.W.H.L., H.P., H.Y., S.C.L.); University of Southern California Research Center for Liver Diseases, Keck School of Medicine, Los Angeles, California (T.W.H.L., H.P., H.Y., S.K., P.P., S.C.L.); Department of Pediatric Gastroenterology, Hepatology, and Nutrition, Children's Hospital Los Angeles, Los Angeles, California (Y.Z.); and CIC bioGUNE, Ciberehd, Bizkaia, Spain (J.M.M.).
Shelly C LuDivision of Gastroenterology, Cedars Sinai Medical Center, Los Angeles, California (T.W.H.L., H.P., H.Y., S.C.L.); University of Southern California Research Center for Liver Diseases, Keck School of Medicine, Los Angeles, California (T.W.H.L., H.P., H.Y., S.K., P.P., S.C.L.); Department of Pediatric Gastroenterology, Hepatology, and Nutrition, Children's Hospital Los Angeles, Los Angeles, California (Y.Z.); and CIC bioGUNE, Ciberehd, Bizkaia, Spain (J.M.M.) Shelly.lu@cshs.org.
University of Southern California · USCedars-Sinai Medical Center · USChildren's Hospital of Los Angeles · USCIC bioGUNE · ES

Funding

USC RESEARCH CENTER FOR LIVER DISEASES: PILOT PROGRAMSP30DK048522 · NIDDK · UNIVERSITY OF SOUTHERN CALIFORNIA · PI GOLDEN, LUCY MARY · 1995 to 2020
$21.8M
Role of SAMe in Pathogenesis and Treatment of Non-Alcholic Fatty Liver DiseaseR01AT001576 · NCCIH · UNIVERSITY OF SOUTHERN CALIFORNIA · PI LU, SHELLY CHI-LOO · 2002 to 2018
$5.0M
Role of MAT and SAMe in Colon Cancer Pathogenesis and TreatmentR01AT004896 · NCCIH · UNIVERSITY OF SOUTHERN CALIFORNIA · PI LU, SHELLY CHI-LOO · 2008 to 2012
$2.0M
NCCIH NIH HHS R01 AT001576NCCIH NIH HHS R01-AT001576NCCIH NIH HHS R01 AT004896NCCIH NIH HHS R01-AT004896NIDDK NIH HHS P30 DK048522NIDDK NIH HHS P30-DK48522
6 · The paper itself

Abstract

S-Adenosylmethionine (SAMe), the principal methyl donor that is available as a nutritional supplement, and its metabolite methylthioadenosine (MTA) exert chemopreventive properties against liver and colon cancer in experimental models. Both agents reduced β-catenin expression on immunohistochemistry in a murine colitis-associated colon cancer model. In this study, we examined the molecular mechanisms involved. SAMe or MTA treatment in the colitis-associated cancer model lowered total β-catenin protein levels by 47 and 78%, respectively. In an orthotopic liver cancer model, increasing SAMe levels by overexpressing methionine adenosyltransferase 1A also reduced total β-catenin levels by 68%. In both cases, lower cyclin D1 and c-Myc expression correlated with lower β-catenin levels. In liver (HepG2) and colon (SW480, HCT116) cancer cells with constitutively active β-catenin signaling, SAMe and MTA treatment inhibited β-catenin activity by excluding it from the nuclear compartment. However, in liver (Huh-7) and colon (RKO) cancer cells expressing wild-type Wnt/β-catenin, SAMe and MTA accelerated β-catenin degradation by a glycogen synthase kinase 3-β-dependent mechanism. Both agents lowered protein kinase B activity, but this was not mediated by inhibiting phosphoinositide 3-kinase. Instead, both agents increased the activity of protein phosphatase 2A, which inactivates protein kinase B. The effect of MTA on lowering β-catenin is direct and not mediated by its conversion to SAMe, as blocking this conversion had no influence. In conclusion, SAMe and MTA inhibit Wnt/β-catenin signaling in colon and liver cancer cells regardless of whether this pathway is aberrantly induced, making them ideal candidates for chemoprevention and/or chemotherapy in these cancers.

Indexed as

Animalsbeta CateninCell Line, TumorColonic NeoplasmsDeoxyadenosinesGene Expression Regulation, NeoplasticHCT116 CellsHep G2 CellsHumansLiver NeoplasmsMiceNeoplasms, ExperimentalS-AdenosylmethionineSignal TransductionThionucleosides5'-methylthioadenosinebeta CateninDeoxyadenosinesS-AdenosylmethionineThionucleosides

Identifiers

PMID25338671
PMCPMC4279083
OpenAlexW2117250001

What OpenQuestion holds

Textmetadata
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.