Dataset Information

Resveratrol reduces prostate cancer growth and metastasis by inhibiting the Akt/MicroRNA-21 pathway.

ABSTRACT: The consumption of foods containing resveratrol produces significant health benefits. Resveratrol inhibits cancer by reducing cell proliferation and metastasis and by inducing apoptosis. These actions could be explained by its ability to inhibit (ERK-1/2), Akt and suppressing the levels of estrogen and insulin growth factor -1 (IGF-1) receptor. How these processes are manifested into the antitumor actions of resveratrol is not clear. Using microarray studies, we show that resveratrol reduced the expression of various prostate-tumor associated microRNAs (miRs) including miR-21 in androgen-receptor negative and highly aggressive human prostate cancer cells, PC-3M-MM2. This effect of resveratrol was associated with reduced cell viability, migration and invasiveness. Additionally, resveratrol increased the expression of tumor suppressors, PDCD4 and maspin, which are negatively regulated by miR-21. Short interfering (si) RNA against PDCD4 attenuated resveratrol's effect on prostate cancer cells, and similar effects were observed following over expression of miR-21 with pre-miR-21 oligonucleotides. PC-3M-MM2 cells also exhibited high levels of phospho-Akt (pAkt), which were reduced by both resveratrol and LY294002 (a PI3-kinase inhibitor). MiR-21 expression in these cells appeared to be dependent on Akt, as LY294002 reduced the levels of miR-21 along with a concurrent increase in PDCD4 expression. These in vitro findings were further corroborated in a severe combined immunodeficient (SCID) mouse xenograft model of prostate cancer. Oral administration of resveratrol not only inhibited the tumor growth but also decreased the incidence and number of metastatic lung lesions. These tumor- and metastatic-suppressive effects of resveratrol were associated with reduced miR-21 and pAkt, and elevated PDCD4 levels. Similar anti-tumor effects of resveratrol were observed in DU145 and LNCaP prostate cancer cells which were associated with suppression of Akt and PDCD4, but independent of miR-21.These data suggest that resveratrol's anti-tumor actions in prostate cancer could be explained, in part, through inhibition of Akt/miR-21 signaling pathway.

SUBMITTER: Sheth S

PROVIDER: S-EPMC3521661 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Resveratrol reduces prostate cancer growth and metastasis by inhibiting the Akt/MicroRNA-21 pathway.

Sheth Sandeep S Jajoo Sarvesh S Kaur Tejbeer T Mukherjea Debashree D Sheehan Kelly K Rybak Leonard P LP Ramkumar Vickram V

PloS one 20121213 12

The consumption of foods containing resveratrol produces significant health benefits. Resveratrol inhibits cancer by reducing cell proliferation and metastasis and by inducing apoptosis. These actions could be explained by its ability to inhibit (ERK-1/2), Akt and suppressing the levels of estrogen and insulin growth factor -1 (IGF-1) receptor. How these processes are manifested into the antitumor actions of resveratrol is not clear. Using microarray studies, we show that resveratrol reduced the ...[more]

PMID: 23272133

Similar Datasets

Project description:BackgroundEukaryotic initiation factor 3 (eIF3) is the largest translation initiation factor, and oncogenic roles have been discovered for its subunits, including the f subunit (ie, eIF3f), in various human cancers. However, the roles of eIF3f in the development and progression of prostate cancer (PCa) have not been reported.Materials and methodsWe performed in silico analysis to screen the expression of eIF3 subunits. Relevant shRNAs were used to knock down eIF3 subunits in 22Rv1 cells and cell proliferation was analyzed. eIF3f expression in PCa specimens was confirmed by immunohistochemistry. eIF3f knockdown was established to evaluate the effects of eIF3f on cell proliferation in vitro and in vivo. RNA-seq, bioinformatics analysis and Western blotting were applied to explore the molecular details underlying the biological function of eIF3f in PCa cells. shRNA-resistant eIF3f and myristoylated-Akt were used to rescue the effects of eIF3f disturbance on PCa cells.ResultsFunctional analyses confirmed that eIF3f is essential for PCa proliferation. Notably, the expression of eIF3f was found to be elevated in human PCa tissues as well as in PCa cell lines. eIF3f silencing significantly suppressed the growth of PCa cells, both in vitro and in vivo. eIF3f expression was positively correlated with Akt signaling activity in RNA-seq profiles and published prostate cohorts. Knockdown of eIF3f markedly reduced the levels of phosphorylated Akt in PCa cells. Exogenous expression of shRNA-resistant eIF3f in eIF3f knockdown cells restored Akt phosphorylation levels and cell growth. Importantly, rescue experiments revealed that ectopic expression of myristoylated-Akt partially alleviated the suppressive effects of eIF3f disturbance with respect to the growth of PCa cells.ConclusionThese results suggested that eIF3f has an oncogenic role in PCa, mediated at least partially through the regulation of Akt signaling, and that eIF3f represents a potential target for the inhibition of PCa growth and progression.

Dataset Information

Resveratrol reduces prostate cancer growth and metastasis by inhibiting the Akt/MicroRNA-21 pathway.

Publications

Resveratrol reduces prostate cancer growth and metastasis by inhibiting the Akt/MicroRNA-21 pathway.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets