RGD Reference Report - Apigenin attenuates insulin-like growth factor-I signaling in an autochthonous mouse prostate cancer model. - Rat Genome Database

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Apigenin attenuates insulin-like growth factor-I signaling in an autochthonous mouse prostate cancer model.

Authors: Shukla, Sanjeev  MacLennan, Gregory T  Fu, Pingfu  Gupta, Sanjay 
Citation: Shukla S, etal., Pharm Res. 2012 Jun;29(6):1506-17. doi: 10.1007/s11095-011-0625-0. Epub 2011 Dec 3.
RGD ID: 13504820
Pubmed: PMID:22139534   (View Abstract at PubMed)
PMCID: PMC4017263   (View Article at PubMed Central)
DOI: DOI:10.1007/s11095-011-0625-0   (Journal Full-text)


PURPOSE: Deregulation of IGF signaling plays an important role in prostate cancer and contributes to invasion and metastasis. We determined the effect of apigenin, a plant flavone, on IGF signaling and its downstream targets in TRAMP mice.
METHODS: Mice received p.o. apigenin at 20 and 50 µg/day dose for 20 weeks. ELISA, Western blotting and immunohistochemistry were performed to examine the IGF-axis and its regulated pathway in response to apigenin intake.
RESULTS: Increased serum levels of IGF-I, VEGF, uPA and concomitant decrease in IGFBP-3 were observed; p-Akt (Ser473), p-ERK1 (T202/Y204) and p-ERK2 (T185/Y187) expression increased in the dorso-lateral prostate of TRAMP mice during the course of cancer progression as a function of age. P.o. administration of apigenin resulted in substantial reduction in the levels of IGF-I and increase in the levels of IGFBP-3 in the serum and the dorso-lateral prostate. This modulation of IGF/IGFBP-3 was associated with an inhibition of p-Akt and p-ERK1/2. Apigenin intake resulted in marked inhibition of VEGF, uPA, MMP-2 and MMP-9 which coincided with tumor growth inhibition and complete absence of metastasis in TRAMP mice.
CONCLUSIONS: Our results indicate that apigenin effectively suppressed prostate cancer progression in TRAMP mice by attenuating IGF-I/IGFBP-3 signaling and inhibiting angiogenesis and metastasis.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Neoplasm Metastasis treatmentISOMapk1 (Mus musculus)13504820; 13504820associated with prostate adenocarcinomaRGD 
Neoplasm Metastasis treatmentIDA 13504820associated with prostate adenocarcinomaRGD 
prostate adenocarcinoma treatmentISOMapk1 (Mus musculus)13504820; 13504820 RGD 
prostate adenocarcinoma treatmentIDA 13504820 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Mapk1  (mitogen activated protein kinase 1)

Genes (Mus musculus)
Mapk1  (mitogen-activated protein kinase 1)

Genes (Homo sapiens)
MAPK1  (mitogen-activated protein kinase 1)


Additional Information