Involvement of the cAMP/protein kinase A pathway and of mitogen-activated protein kinase in the anti-proliferative effects of anandamide in human breast cancer cells
Open accessAbstract
Anandamide (ANA) inhibits prolactin‐ and nerve growth factor (NGF)‐induced proliferation of human breast cancer cells by decreasing the levels of the 100 kDa prolactin receptor (PRLr) and the high affinity trk NGF receptor, respectively, and by acting via CB 1‐like cannabinoid receptors. However, the intracellular signals that mediate these effects are not known. Here, we show that, in MCF‐7 cells: (i) forskolin and the mitogen‐activated protein kinase (MAPK) kinase inhibitor PD098059 prevent, and the protein kinase A inhibitor RpcAMPs mimics, the inhibitory effects of ANA on cell proliferation and PRLr/trk expression and (ii) ANA inhibits forskolin‐induced cAMP formation and stimulates Raf‐1 translocation and MAPK activity, in a fashion sensitive to the selective CB 1 antagonist SR141716A. ANA stimulation of MAPK was enhanced by inhibitors of ANA hydrolysis. Forskolin inhibited MAPK and ANA‐induced Raf‐1 translocation. These findings indicate that, in MCF‐7 cells, ANA inhibits adenylyl cyclase and activates MAPK, thereby exerting a down‐regulation on PRLr and trk levels and a suppression of cell proliferation.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The PKA activator forskolin inhibits MAPK-induced raf-1 translocation.
“the PKA activator forskolin inhibits MAPK-induced raf-1 translocation118”
From Cytokines and Glucocorticoid Receptor Signaling (2009) · cites this paper as [118]
Section 3.3 reports that forskolin prevented anandamide (ANA)-induced Raf-1 translocation in MCF-7 cells. It does not describe the translocation as MAPK-induced; instead, it reports ANA-induced Raf-1 translocation alongside MAPK activation. Page numbers are not provided in our copy's passages. (LLM, conf=0.85)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
No citation lists for this paper
No citation lists for this paper yet — checked again daily.
References 30 · Cited by 168
Research works printed but not linked: 5
- De Petrocellis, L., Melck, D., Palmisano, A., Bisogno, T., Laez- za, C., Bifulco, M. and Di Marzo, V. (1998) Proc. Natl. Acad. Sci. USA 95, 8375^8380.
- Melck, D., De Petrocellis, L., Orlando, P., Bisogno, T., Laezza, C., Bifulco, M. and Di Marzo, V. (1999) Endocrinology (in press).
- Ehrhard, P.B., Ganter, U., Stalder, A., Bauer, J. and Otten, U. (1993) Proc. Natl. Acad. Sci. USA 90, 5423^5427.
- Rosenbaum, T., Vidaltamayo, R., Sanchez-SotoMa, C., Zentella, A. and Hiriart, M. (1998) Proc. Natl. Acad. Sci. USA 95, 7784^ 7788.
- Chen, J., Bander, J.A., Santore, T.A., Chen, Y., Ram, P.T., Smit, M.J. and Iyengar, R. (1998) Proc. Natl. Acad. Sci. USA 95, 2648^2652.
- Authors
- Melck, D., Rueda, D., Galve-Roperh, I., De Petrocellis, L., Guzmán, M., & Di Marzo, V.
- Affiliations
- National Research Council (IT)
- Universidad Complutense de Madrid (ES)
- Venue
- FEBS Letters
- Publisher
- Wiley
- Published
- 1999-12-17
- Volume
- 463
- Issue
- 3
- Pages
- 235-240
- ISSN
- 0014-5793 (ISSN-L)
- 1873-3468
- OpenAlex
- W2055037794
- Cited by
- 168
- References
- 30
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 3 · 2022: 3 · 2021: 5 · 2020: 6 · 2019: 6 · 2018: 5 · 2017: 9 · 2016: 6 · 2015: 6 · 2014: 5 · 2013: 5 · 2012: 5
- FWCI
- 5.37
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- FEBS Letters (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Keywords
- anandamide, breast cancer, cAMP/protein kinase A pathway, mitogen-activated protein kinase, CB1 receptor, prolactin receptor, cell proliferation, MCF-7 cells, adenylate cyclase, SR141716A, PD98059, forskolin, endocannabinoids
- MeSH terms
- Rimonabant, Cyclic AMP, Arachidonic Acids, Breast Neoplasms, Cell Division, Cell Line, Flavonoids, Colforsin, Humans, Piperidines, Prolactin, Pyrazoles, Receptors, Prolactin, Tumor Cells, Cultured, Down-Regulation, Cyclic AMP-Dependent Protein Kinases, Proto-Oncogene Proteins c-raf, Mitogen-Activated Protein Kinases, Nerve Growth Factor, Polyunsaturated Alkamides, Endocannabinoids
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
