Retigeric Acid b exhibits antitumor activity through suppression of nuclear factor-κB signaling in prostate cancer cells in vitro and in vivo

Yong Qing Liu, Xiao Yan Hu, Tao Lu, Yan Na Cheng, Charles Y F Young, Hui Qing Yuan, Hong Xiang Lou

Research output: Contribution to journalArticle

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Abstract

Previously, we reported that retigeric acid B (RB), a natural pentacyclic triterpenic acid isolated from lichen, inhibited cell growth and induced apoptosis in androgen-independent prostate cancer (PCa) cells. However, the mechanism of action of RB remains unclear. In this study, we found that using PC3 and DU145 cells as models, RB inhibited phosphorylation levels of IκBα and p65 subunit of NF-κB in a time- and dosage-dependent manner. Detailed study revealed that RB blocked the nuclear translocation of p65 and its DNA binding activity, which correlated with suppression of NF-κB-regulated proteins including Bcl-2, Bcl-xL, cyclin D1 and survivin. NF-κB reporter assay suggested that RB was able to inhibit both constitutive activated-NF-κB and LPS (lipopolysaccharide)-induced activation of NF-κB. Overexpression of RelA/p65 rescued RB-induced cell death, while knockdown of RelA/p65 significantly promoted RB-mediated inhibitory effect on cell proliferation, suggesting the crucial involvement of NF-κB pathway in this event. We further analyzed antitumor activity of RB in in vivo study. In C57BL/6 mice carrying RM-1 homografts, RB inhibited tumor growth and triggered apoptosis mainly through suppressing NF-κB activity in tumor tissues. Additionally, DNA microarray data revealed global changes in the gene expression associated with cell proliferation, apoptosis, invasion and metastasis in response to RB treatment. Therefore, our findings suggested that RB exerted its anti-tumor effect by targeting the NF-κB pathway in PCa cells, and this could be a general mechanism for the anti-tumor effect of RB in other types of cancers as well.

Original languageEnglish
Article numbere38000
JournalPLoS One
Volume7
Issue number5
DOIs
StatePublished - May 29 2012

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prostatic neoplasms
Prostatic Neoplasms
Cells
Acids
acids
Tumors
neoplasms
Cell proliferation
apoptosis
Neoplasms
Apoptosis
neoplasm cells
retigeric acid B
In Vitro Techniques
cell proliferation
Cell Proliferation
Lichens
Phosphorylation
DNA
Cyclin D1

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Retigeric Acid b exhibits antitumor activity through suppression of nuclear factor-κB signaling in prostate cancer cells in vitro and in vivo. / Liu, Yong Qing; Hu, Xiao Yan; Lu, Tao; Cheng, Yan Na; Young, Charles Y F; Yuan, Hui Qing; Lou, Hong Xiang.

In: PLoS One, Vol. 7, No. 5, e38000, 29.05.2012.

Research output: Contribution to journalArticle

Liu, Yong Qing ; Hu, Xiao Yan ; Lu, Tao ; Cheng, Yan Na ; Young, Charles Y F ; Yuan, Hui Qing ; Lou, Hong Xiang. / Retigeric Acid b exhibits antitumor activity through suppression of nuclear factor-κB signaling in prostate cancer cells in vitro and in vivo. In: PLoS One. 2012 ; Vol. 7, No. 5.
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