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The adipocyte-derived hormone leptin has proliferative actions on androgen-resistant prostate cancer cells linking obesity to advanced stages of prostate cancer.

Hoda MR, Theil G, Mohammed N, Fischer K, Fornara P - J Oncol (2012)

Bottom Line: Background.Further, Western blotting was applied to detect the phosphorylation of an ERK1/2, and a specific inhibitor of MAPK (PD98059; 40 μM) was used.Results.

View Article: PubMed Central - PubMed

Affiliation: Clinic for Urology and Kidney Transplantation Centre, University Medical School of Halle/Wittenberg, Ernst-Grube-Strasse 40, 06120 Halle, Saale, Germany.

ABSTRACT
Background. Because obesity may be a risk factor for prostate cancer, we investigated proliferative effects of adipocytes-derived hormone leptin on human prostate cancer cells and assessed the role of mitogen-activated protein kinase (MAPK) signaling pathway in mediating these actions. Material and Methods. Three human prostate cancer cell lines were treated with increasing doses of recombinant leptin. Cell growth was measured under serum-free conditions using a spectrophotometric assay. Further, Western blotting was applied to detect the phosphorylation of an ERK1/2, and a specific inhibitor of MAPK (PD98059; 40 μM) was used. Results. In both androgen-resistant cell lines DU145 and PC-3, cell growth was dose-dependently increased by leptin after 24 hrs and 48 hrs of incubation, whereas leptin's proliferative effects on androgen-sensitive cell line LNCaP was less pronounced. Further, leptin caused dose-dependent ERK1/2 phosphorylation in both androgen-resistant cell lines, and pretreatment of these cells with PD98059 inhibited these responses. Conclusions. Leptin may be a potential link between obesity and risk of progression of prostate cancer. Thus, studies on leptin and obesity association to prostate cancer should differentiate patients according to androgen sensitivity.

No MeSH data available.


Related in: MedlinePlus

Inhibitor of MAPK attenuates leptin-induced prostate cancer cell growth in androgen-resistant prostate cancer cell lines. Cells ((a); PC-3, (b); DU145) were cultured in serum-free media for 24 and 48 hours with or without leptin (100 ng/mL). Before adding leptin, cells were pretreated with the MEK inhibitor PD98059 (PD; 40 μM). Cell number was determined by the colorimetric XTT assay. Assays were performed at least five times and samples were run in triplicate. The data (means ± SEM) are reported as percentage of the untreated control and asterisks denote values significantly different from vehicle-treated cells. (*P < 0.05; **P < 0.01; ***P < 0.001 by ANOVA).
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fig3: Inhibitor of MAPK attenuates leptin-induced prostate cancer cell growth in androgen-resistant prostate cancer cell lines. Cells ((a); PC-3, (b); DU145) were cultured in serum-free media for 24 and 48 hours with or without leptin (100 ng/mL). Before adding leptin, cells were pretreated with the MEK inhibitor PD98059 (PD; 40 μM). Cell number was determined by the colorimetric XTT assay. Assays were performed at least five times and samples were run in triplicate. The data (means ± SEM) are reported as percentage of the untreated control and asterisks denote values significantly different from vehicle-treated cells. (*P < 0.05; **P < 0.01; ***P < 0.001 by ANOVA).

Mentions: To further investigate whether leptin-stimulated MAPK activation is linked to cell proliferation in androgen-resistant cells, a specific inhibitor was used to block this signaling pathway. Leptin alone increased cell proliferation in both androgen-resistant cell lines. However, pretreatment of cell lines with the MEK inhibitor PD98059 (40 μM) markedly reduced cell proliferation in both cell lines (Figures 3(a) and 3(b)).


The adipocyte-derived hormone leptin has proliferative actions on androgen-resistant prostate cancer cells linking obesity to advanced stages of prostate cancer.

Hoda MR, Theil G, Mohammed N, Fischer K, Fornara P - J Oncol (2012)

Inhibitor of MAPK attenuates leptin-induced prostate cancer cell growth in androgen-resistant prostate cancer cell lines. Cells ((a); PC-3, (b); DU145) were cultured in serum-free media for 24 and 48 hours with or without leptin (100 ng/mL). Before adding leptin, cells were pretreated with the MEK inhibitor PD98059 (PD; 40 μM). Cell number was determined by the colorimetric XTT assay. Assays were performed at least five times and samples were run in triplicate. The data (means ± SEM) are reported as percentage of the untreated control and asterisks denote values significantly different from vehicle-treated cells. (*P < 0.05; **P < 0.01; ***P < 0.001 by ANOVA).
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3368429&req=5

fig3: Inhibitor of MAPK attenuates leptin-induced prostate cancer cell growth in androgen-resistant prostate cancer cell lines. Cells ((a); PC-3, (b); DU145) were cultured in serum-free media for 24 and 48 hours with or without leptin (100 ng/mL). Before adding leptin, cells were pretreated with the MEK inhibitor PD98059 (PD; 40 μM). Cell number was determined by the colorimetric XTT assay. Assays were performed at least five times and samples were run in triplicate. The data (means ± SEM) are reported as percentage of the untreated control and asterisks denote values significantly different from vehicle-treated cells. (*P < 0.05; **P < 0.01; ***P < 0.001 by ANOVA).
Mentions: To further investigate whether leptin-stimulated MAPK activation is linked to cell proliferation in androgen-resistant cells, a specific inhibitor was used to block this signaling pathway. Leptin alone increased cell proliferation in both androgen-resistant cell lines. However, pretreatment of cell lines with the MEK inhibitor PD98059 (40 μM) markedly reduced cell proliferation in both cell lines (Figures 3(a) and 3(b)).

Bottom Line: Background.Further, Western blotting was applied to detect the phosphorylation of an ERK1/2, and a specific inhibitor of MAPK (PD98059; 40 μM) was used.Results.

View Article: PubMed Central - PubMed

Affiliation: Clinic for Urology and Kidney Transplantation Centre, University Medical School of Halle/Wittenberg, Ernst-Grube-Strasse 40, 06120 Halle, Saale, Germany.

ABSTRACT
Background. Because obesity may be a risk factor for prostate cancer, we investigated proliferative effects of adipocytes-derived hormone leptin on human prostate cancer cells and assessed the role of mitogen-activated protein kinase (MAPK) signaling pathway in mediating these actions. Material and Methods. Three human prostate cancer cell lines were treated with increasing doses of recombinant leptin. Cell growth was measured under serum-free conditions using a spectrophotometric assay. Further, Western blotting was applied to detect the phosphorylation of an ERK1/2, and a specific inhibitor of MAPK (PD98059; 40 μM) was used. Results. In both androgen-resistant cell lines DU145 and PC-3, cell growth was dose-dependently increased by leptin after 24 hrs and 48 hrs of incubation, whereas leptin's proliferative effects on androgen-sensitive cell line LNCaP was less pronounced. Further, leptin caused dose-dependent ERK1/2 phosphorylation in both androgen-resistant cell lines, and pretreatment of these cells with PD98059 inhibited these responses. Conclusions. Leptin may be a potential link between obesity and risk of progression of prostate cancer. Thus, studies on leptin and obesity association to prostate cancer should differentiate patients according to androgen sensitivity.

No MeSH data available.


Related in: MedlinePlus