RGD Reference Report - Inhibitory effect of 2-(piperidinoethoxyphenyl)-3-(4-hydroxyphenyl)-2H-benzo(b)pyran (K-1) on human primary endometrial hyperplasial cells mediated via combined suppression of Wnt/ß-catenin signaling and PI3K/Akt survival pathway. - Rat Genome Database

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Inhibitory effect of 2-(piperidinoethoxyphenyl)-3-(4-hydroxyphenyl)-2H-benzo(b)pyran (K-1) on human primary endometrial hyperplasial cells mediated via combined suppression of Wnt/ß-catenin signaling and PI3K/Akt survival pathway.

Authors: Chandra, V  Fatima, I  Manohar, M  Popli, P  Sirohi, V K  Hussain, M K  Hajela, K  Sankhwar, P  Dwivedi, A 
Citation: Chandra V, etal., Cell Death Dis. 2014 Aug 21;5:e1380. doi: 10.1038/cddis.2014.334.
RGD ID: 13432159
Pubmed: PMID:25144715   (View Abstract at PubMed)
PMCID: PMC4454309   (View Article at PubMed Central)
DOI: DOI:10.1038/cddis.2014.334   (Journal Full-text)

Endometrial hyperplasia is a precursor to the most common gynecologic cancer diagnosed in women. Apart from estrogenic induction, aberrant activation of the Wnt/ß-catenin signal is well known to correlate with endometrial hyperplasia and its carcinoma. The benzopyran compound 2-(piperidinoethoxyphenyl)-3-(4-hydroxyphenyl)-2H-benzo (b) pyran(K-1), a potent antiestrogenic agent, has been shown to have apoptosis-inducing activity in rat uterine hyperplasia. The current study was undertaken to explore the effect of the benzopyran compound K-1 on growth and Wnt signaling in human endometrial hyperplasial cells. Primary culture of atypical endometrial hyperplasial cells was characterized by the epithelial cell marker cytokeratin-7. Results revealed that compound K-1 reduced the viability of primary endometrial hyperplasial cells and expression of ERα, PR, PCNA, Wnt7a, FZD6, pGsk3ß and ß-catenin without affecting the growth of the primary culture of normal endometrial cells. The ß-catenin target genes CyclinD1 and c-myc were also found to be reduced, whereas the expression of axin2 and Wnt/ß-catenin signaling inhibitor Dkk-1 was found to be upregulated, which caused the reduced interaction of Wnt7a and FZD6. Nuclear accumulation of ß-catenin was found to be decreased by compound K-1. K-1 also suppressed the pPI3K/pAkt survival pathway and induced the cleavage of caspases and PARP, thus subsequently causing the apoptosis of endometrial hyperplasial cells. In conclusion, compound K-1 suppressed the growth of human primary endometrial hyperplasial cells through discontinued Wnt/ß-catenin signaling and induced apoptosis via inhibiting the PI3K/Akt survival pathway.

Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
endometrial cancer pathway   IEP 13432159 RGD 
endometrial cancer pathway   ISOAXIN2 (Homo sapiens)13432159; 13432159 RGD 
Objects Annotated

Genes (Rattus norvegicus)
Axin2  (axin 2)

Genes (Mus musculus)
Axin2  (axin 2)

Genes (Homo sapiens)
AXIN2  (axin 2)


Additional Information