Upregulation of prostate‐derived Ets factor by luteolin causes inhibition of cell proliferation and cell invasion in prostate carcinoma cells

Abstract

Luteolin is a polyphenolic flavone and has antitumor activity for many cancers. The prostate-derived Ets factor (PDEF), a novel epithelium-specific Ets transcription factor, acts as an androgen-independent transcriptional activator of the prostate-specific antigen (PSA) promoter. We determined the antitumor function of luteolin via upregulation of PDEF gene expression in human prostate carcinoma LNCaP cells. Results from flow cytometry and Prostate derived Ets transcription factor (PDEF), a novel epithelium-specific Ets transcription factor, not only acts as an androgen-independent transcriptional activator of the prostate-specific antigen (PSA) promoter but also directly interacts with the DNA binding domain of androgen receptors (ARs) and enhances androgen-mediated activation of the PSA promoter.1 Studies indicate that silibinin and tectorigenin treatments decrease PSA secretion in human LNCaP cells through the downregulation of PDEF gene expression.2,3 Furthermore, transient overexpression of PDEF enhances PSA gene expression at the transcriptional and translational levels under androgen-free condition; however, curcumin treatments block PSA gene expression by a mechanism other than inhibition of the PDEF gene expression. 4,5 A recent study using proteomic analysis identified 286 proteins in the PDEF-associated protein complex involved in the cell cycle, DNA repair, cytoskeleton organization, mRNA processing and cell signaling in MDA-MB-231 human breast cancer cells. 6 A global gene expression analysis identified several genes, which are associated with PDEF expression, regulating cell migration during cancer progression. 7 In vitro and xenograft studies revealed that PDEF knock-down in prostate LNCaP and PC-3 cancer cells increased migration and invasiveness suggesting that PDEF is involved in the tumor biology of the human prostate. 8 Expression of B-cell translocation gene 2 (BTG2) in cycling cells induced accumulation of growth-inhibitory forms of pRb and led to G1 cell-cycle arrest.9 BTG2 is more abundantly expressed in prostate tissue with high epithelial

Growth differentiation factor-15 upregulates interleukin-6 to promote tumorigenesis of prostate carcinoma PC-3 cells

“…The GDF15 primers (5 0 -GGCCAACCAGAGCTGG-GAAG-3 0 and 5 0 -GCCCGAGAGATACGCAGGT G-3 0 ) were used to amplify sequences specific to human GDF15 mRNA. The sequence of primers used to amplify sequences specific to human maspin, N-myc downstream-regulated gene 1 (NDRG1), matriptase, IL6, and b-actin were previously described (Tsui et al 2008a(Tsui et al , 2011b(Tsui et al , 2012a. After separation by 2% agarose gel electrophoresis, the PCR products were visualized by ethidium bromide staining.…”

“…Equal quantities of cell extract were loaded onto a 10% SDS-polyacrylamide gel and analyzed using the Western lightning plus-ECL detection system (PerkinElmer, Inc., Waltham, MA, USA) as described previously (Tsui et al 2012a). The blotting membranes were probed with 1:5000 diluted polyclonal matriptase antiserum (IM1014; Calbiochem, Darmstadt, Germany), 1:1000 diluted maspin antiserum (554292; BD Biosciences, Bedford, MA, USA), 1:5000 diluted NDRG1 antiserum (N-19; Santa Cruz Biotechnology), 1:500 diluted GDF15 antiserum (07-217; Upstate Biotechnology, Charlottesville, VA, USA), or 1:1000 diluted antib-actin antiserum (C11, Santa Cruz Biotechnology).…”

“…The human IL6 reporter vector, maspin reporter vector, and NDRG1 reporter vector were constructed as previously described (Tsui et al 2008b(Tsui et al , 2012a.…”

Expression of prostate stem cell antigen is downregulated during flavonoid-induced cytotoxicity in prostate cancer cells

“…Flavonoids are principally categorized into flavones, flavonols, flavanols, flavanones, flavanonols and isoflavones (13,14). Genistein (isoflavone), luteolin (flavone) and quercetin (flavonol) are typically present in numerous fruits and vegetables, and have been shown to inhibit cell proliferation with variable efficacy in human prostate cancer (15)(16)(17). Consistent with these findings, the present study observed that genistein, luteolin and quercetin inhibited the proliferation of prostate cancer cells in a dose-dependent manner and in the following order of potency: Genistein>luteolin>quercetin.…”

Relative mRNA expression of prostate-derived E-twenty-six factor and E-twenty-six variant 4 transcription factors, and of uridine phosphorylase-1 and thymidine phosphorylase enzymes, in benign and malignant prostatic tissue

“…The prostate-derived ETS factor (PDEF) is limited to tissues that are of epithelial origin and are hormone-regulated, such as prostate, breast, salivary glands, ovaries, colon, airways and stomach tissues (7,(10)(11)(12)(13)(14)(15). In the prostate, PDEF is predominantly expressed in the luminal epithelium, acting as an activator of the transcription of prostate-specific antigen (PSA), either in the androgen-sensitive or androgen-independent setting (16)(17)(18). ETS variant 4 (ETV4) may be involved in chromosomal translocations in human Relative mRNA expression of prostate-derived E-twenty-six factor and E-twenty-six variant 4 transcription factors, and of uridine phosphorylase-1 and thymidine phosphorylase enzymes, in benign and malignant prostatic tissue LUCIANE ROSTIROLA CAVAZZOLA 1* , GUSTAVO FRANCO CARVALHAL 2* , CANDIDA DEVES 1 ,…”