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Cited by 225Sirtuins and Resveratrol in MedicineMicroRNA in disease regulationMetabolism, Diabetes, and Cancer

Resveratrol Reduces Prostate Cancer Growth and Metastasis by Inhibiting the Akt/MicroRNA-21 Pathway

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Sheth, Sandeep, Jajoo, Sarvesh, Kaur, Tejbeer, Mukherjea, Debashree, Sheehan, Kelly, Rybak, Leonard P., Ramkumar, Vickram·2012·PLoS ONE
DOI 10.1371/journal.pone.0051655PMC PMC3521661
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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.

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  • Curcumin and resveratrol up-regulate PDCD4-protein levels by inhibiting miR21 expression.

    “Both compounds up-regulate PDCD4-protein levels by inhibiting mir21 expression [93,94,95,96].”

    From Control Mechanisms of the Tumor Suppressor PDCD4: Expression and Functions (2019) · cites this paper as [96]

    The Results section reports that resveratrol reduced miR-21 expression and increased PDCD4 protein in PC-3M-MM2 cells; pre-miR-21 also attenuated resveratrol’s effect on PDCD4. The provided passages do not establish the curcumin half of the sentence. They also note that resveratrol increased PDCD4 in two other cell lines without inhibiting miR-21 there. Page numbers were not provided. (LLM, conf=0.88)

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Authors
Sheth, S., Jajoo, S., Kaur, T., Mukherjea, D., Sheehan, K., Rybak, L. P., & Ramkumar, V.
Affiliations
SIU Medicine (US)
Corresponding author
Ramkumar, Vickram
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2012-12-13
Volume
7
Issue
12
Pages
e51655
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0051655
PMC
PMC3521661
OpenAlex
W2059378007
Cited by
225
References
59
Citations by year
2026: 7 · 2025: 16 · 2024: 9 · 2023: 8 · 2022: 11 · 2021: 16 · 2020: 17 · 2019: 19 · 2018: 16 · 2017: 21 · 2016: 26 · 2015: 19 · 2014: 27 · 2013: 12 · 2012: 1
FWCI
9.28
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • Figshare (submittedVersion, cc-by)
Funders
  • U.S. Department of Defense
  • State University of New York
  • School of Medicine, Southern Illinois University
  • National Institutes of Health (5r01dc002396-22)
  • University at Albany
  • National Cancer Institute (R15CA135494)
  • National Institute on Deafness and Other Communication Disorders (R01-DC 002396, R03DC011621)
Topics
  • Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords
resveratrol, prostate cancer, miR-21, Akt signaling, PDCD4, maspin, metastasis, PI3K/Akt signaling, tumor suppressor microRNA, cell migration and invasion, SCID mouse xenograft, anti-tumor effect
MeSH terms
Resveratrol, Animals, Antineoplastic Agents, Cell Survival, Chromones, Enzyme Inhibitors, Estrogens, Flow Cytometry, Humans, Male, Morpholines, Neoplasm Invasiveness, Neoplasm Metastasis, Neoplasm Transplantation, Oligonucleotides, Prostatic Neoplasms, Stilbenes, Wound Healing, Genes, Tumor Suppressor, Mice, SCID, Apoptosis, Receptor, IGF Type 1, RNA, Small Interfering, MicroRNAs, Cell Line, Tumor, Cell Proliferation, Proto-Oncogene Proteins c-akt, Mice

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