Vitamin D Receptor and p21/WAF1 Are Targets of Genistein and 1,25-Dihydroxyvitamin D3 in Human Prostate Cancer Cells

Rao, Anuradha; Coan, April; Welsh, JoEllen; Barclay, Wendy W.; Koumenis, Constantinos; Cramer, Scott D.

doi:10.1158/0008-5472.can-03-3480

Cited by 58 publications

(53 citation statements)

References 18 publications

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“…25 The growth inhibitory effect of 2,2 0 -DHC was observed as early as 24 h following treatment (data not shown). Whereas most of the flavonoids tested were minimally cytotoxic to the PrSC and MCF-7 cell lines, 2,2 0 -DHC was unique in that it was effective at low concentrations on PrSC and MCF-7 cells (IC 50 17.47 and 22.99 mM respectively). The apparent resistance of MCF-7 and PrSC cells to most flavonoids may be a true effect; however, this is difficult to ascertain since all cell lines have been cultured in cell-specific media, and differences in growth media differences may account for some of the observations.…”

Section: Discussionmentioning

confidence: 91%

“…Similarly, ISLQ had greater antiproliferative effect in PCa compared to non-PCa cell lines ( Other flavonoids shown to inhibit proliferation included 5-methoxyflavone, baicalin, baicalein, chrysin and kaempferol as detailed in Table 2. A greater effect on proliferation of LNCaP than PC3 cells were observed with 5-methoxyflavone (IC 50 25.22 and 97.31 mM, respectively). Baicalein had a lower IC 50 than the glycosylated baicalin when tested in LNCaP, while baicalin seemed to be more potent in PC3 than LNCaP.…”

Section: Flavonoids Exert An Antiproliferative Effect On Human Pca Cementioning

confidence: 89%

“…A greater effect on proliferation of LNCaP than PC3 cells were observed with 5-methoxyflavone (IC 50 25.22 and 97.31 mM, respectively). Baicalein had a lower IC 50 than the glycosylated baicalin when tested in LNCaP, while baicalin seemed to be more potent in PC3 than LNCaP. Kaempferol and chrysin had an IC 50 above 40 mM in LNCaP and PC3 cells, a concentration unlikely to be achieved physiologically.…”

Section: Flavonoids Exert An Antiproliferative Effect On Human Pca Cementioning

confidence: 89%

“…[30][31][32] ISLQ, luteolin and quercetin appeared to have greater effect on proliferation in LNCaP than in PC3 cells. In addition, two other flavonoids, 5-methoxyflavone (synthetic) and baicalein (component of PCSPES herbal remedy), had low IC 50 in LNCaP but not PC3 (Table 2). A number of differences between PC3 and LNCaP cells may account for this difference in sensitivity.…”

Section: Discussionmentioning

confidence: 99%

“…Fluorescence was measured on an FL600 fluorescence micro-plate reader (Bio-Tek, VT) with filters set at 480 nm excitation and 520 nm emission. The IC 50 for each flavonoid was determined in the four cell lines tested (Table 2). Each experiment was performed independently at least three times.…”

Section: Cell Proliferation Assaymentioning

confidence: 99%

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Novel antiproliferative flavonoids induce cell cycle arrest in human prostate cancer cell lines

Haddad

Venkateswaran

Viswanathan

et al. 2005

Prostate Cancer Prostatic Dis

151

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Epidemiologic studies have demonstrated an inverse association between flavonoid intake and prostate cancer (PCa) risk. The East Asian diet is very high in flavonoids and, correspondingly, men in China and Japan have the lowest incidence of PCa worldwide. There are thousands of different naturally occurring and synthetic flavonoids. However, only a few have been studied in PCa. Our aim was to identify novel flavonoids with antiproliferative effect in PCa cell lines, as well as determine their effects on cell cycle. We have screened a representative subgroup of 26 flavonoids for antiproliferative effect on the human PCa (LNCaP and PC3), breast cancer (MCF-7), and normal prostate stromal cell lines (PrSC). Using a fluorescence-based cell proliferation assay (Cyquant), we have identified five flavonoids, including the novel compounds 2,2 0 -dihydroxychalcone and fisetin, with antiproliferative and cell cycle arresting properties in human PCa in vitro. Most of the flavonoids tested exerted antiproliferative effect at lower doses in the PCa cell lines compared to the non-PCa cells. Flow cytometry was used as a means to determine the effects on cell cycle. PC3 cells were arrested in G2/M phase by flavonoids. LNCaP cells demonstrated different cell cycle profiles. Further studies are warranted to determine the molecular mechanism of action of 2,2 0 -DHC and fisetin in PCa, and to establish their effectiveness in vivo.

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Section: Discussionmentioning

confidence: 91%

Section: Flavonoids Exert An Antiproliferative Effect On Human Pca Cementioning

confidence: 89%

Section: Flavonoids Exert An Antiproliferative Effect On Human Pca Cementioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Cell Proliferation Assaymentioning

confidence: 99%

See 3 more Smart Citations

Novel antiproliferative flavonoids induce cell cycle arrest in human prostate cancer cell lines

Haddad

Venkateswaran

Viswanathan

et al. 2005

Prostate Cancer Prostatic Dis

151

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Activation of rapid signaling pathways does not contribute to 1α,25‐dihydroxyvitamin D₃‐induced growth inhibition of mouse prostate epithelial progenitor cells

Fleet

Teegarden

2009

J of Cellular Biochemistry

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The active form of vitamin D, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D) inhibits the growth of prostate epithelial cells, however the underlying mechanisms have not been clearly delineated. In the current study, the impact of 1,25(OH)2D on the rapid activation of extracellular-regulated kinase (ERK) 1/2 and protein kinase C α (PKCα), and the role of these pathways in growth inhibition was examined in immortalized mouse prostate epithelial cells, MPEC3, that exhibit stem/progenitor cell characteristics. 1,25(OH)2D treatment suppressed the growth of MPEC3 in a dose and time dependent manner (e.g., 21% reduction at three days with 100 nM 1,25(OH)2D treatment). However, ERK1/2 activity was not altered by 100 nM 1,25(OH)2D treatment for time points from 1 min to 1 h in either serum-containing or serum-free medium. Similarly, PKCα activation (translocation onto the plasma membrane) was not regulated by short-term treatment of 100 nM 1,25(OH)2D. In conclusion, 1,25(OH)2D did not mediate rapid activation of ERK1/2 or PKCα in MPEC3 and therefore the growth inhibitory effect of 1,25(OH)2D is independent of rapid activation of these signaling pathways in this cell type.

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Identification of both Myt-1 and Wee-1 as necessary mediators of the p21-independent inactivation of the cdc-2/cyclin B1 complex and growth inhibition of TRAMP cancer cells by genistein

Touny

Banerjee

2006

Prostate

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Vitamin D Receptor and p21/WAF1 Are Targets of Genistein and 1,25-Dihydroxyvitamin D3 in Human Prostate Cancer Cells

Abstract: ABSTRACT

Cited by 58 publications

References 18 publications

Novel antiproliferative flavonoids induce cell cycle arrest in human prostate cancer cell lines

Novel antiproliferative flavonoids induce cell cycle arrest in human prostate cancer cell lines

Activation of rapid signaling pathways does not contribute to 1α,25‐dihydroxyvitamin D₃‐induced growth inhibition of mouse prostate epithelial progenitor cells

Identification of both Myt-1 and Wee-1 as necessary mediators of the p21-independent inactivation of the cdc-2/cyclin B1 complex and growth inhibition of TRAMP cancer cells by genistein

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Vitamin D Receptor and p21/WAF1 Are Targets of Genistein and 1,25-Dihydroxyvitamin D3 in Human Prostate Cancer Cells

Abstract: ABSTRACT

Cited by 58 publications

References 18 publications

Novel antiproliferative flavonoids induce cell cycle arrest in human prostate cancer cell lines

Novel antiproliferative flavonoids induce cell cycle arrest in human prostate cancer cell lines

Activation of rapid signaling pathways does not contribute to 1α,25‐dihydroxyvitamin D3‐induced growth inhibition of mouse prostate epithelial progenitor cells

Identification of both Myt-1 and Wee-1 as necessary mediators of the p21-independent inactivation of the cdc-2/cyclin B1 complex and growth inhibition of TRAMP cancer cells by genistein

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Activation of rapid signaling pathways does not contribute to 1α,25‐dihydroxyvitamin D₃‐induced growth inhibition of mouse prostate epithelial progenitor cells