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Quercetin inhibits angiogenesis mediated human prostate tumor growth by targeting VEGFR- 2 regulated AKT/mTOR/P70S6K signaling pathways.

Pratheeshkumar P, Budhraja A, Son YO, Wang X, Zhang Z, Ding S, Wang L, Hitron A, Lee JC, Xu M, Chen G, Luo J, Shi X - PLoS ONE (2012)

Bottom Line: Quercetin (20 mg/kg/d) significantly reduced the volume and the weight of solid tumors in prostate xenograft mouse model, indicating that quercetin inhibited tumorigenesis by targeting angiogenesis.Furthermore, quercetin reduced the cell viability and induced apoptosis in prostate cancer cells, which were correlated with the downregulation of AKT, mTOR and P70S6K expressions.Collectively the findings in the present study suggest that quercetin inhibits tumor growth and angiogenesis by targeting VEGF-R2 regulated AKT/mTOR/P70S6K signaling pathway, and could be used as a potential drug candidate for cancer therapy.

View Article: PubMed Central - PubMed

Affiliation: Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, Kentucky, United States of America.

ABSTRACT
Angiogenesis is a crucial step in the growth and metastasis of cancers, since it enables the growing tumor to receive oxygen and nutrients. Cancer prevention using natural products has become an integral part of cancer control. We studied the antiangiogenic activity of quercetin using ex vivo, in vivo and in vitro models. Rat aortic ring assay showed that quercetin at non-toxic concentrations significantly inhibited microvessel sprouting and exhibited a significant inhibition in the proliferation, migration, invasion and tube formation of endothelial cells, which are key events in the process of angiogenesis. Most importantly, quercetin treatment inhibited ex vivo angiogenesis as revealed by chicken egg chorioallantoic membrane assay (CAM) and matrigel plug assay. Western blot analysis showed that quercetin suppressed VEGF induced phosphorylation of VEGF receptor 2 and their downstream protein kinases AKT, mTOR, and ribosomal protein S6 kinase in HUVECs. Quercetin (20 mg/kg/d) significantly reduced the volume and the weight of solid tumors in prostate xenograft mouse model, indicating that quercetin inhibited tumorigenesis by targeting angiogenesis. Furthermore, quercetin reduced the cell viability and induced apoptosis in prostate cancer cells, which were correlated with the downregulation of AKT, mTOR and P70S6K expressions. Collectively the findings in the present study suggest that quercetin inhibits tumor growth and angiogenesis by targeting VEGF-R2 regulated AKT/mTOR/P70S6K signaling pathway, and could be used as a potential drug candidate for cancer therapy.

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Quercetin inhibits tumor growth in a xenograft mouse model.PC-3 cells were injected into 6-week old BALB/cA nude mice (5×106 cells per mouse). After tumors grew to about 100 mm3, mice were treated intraperitoneally with or without quercetin (20 mg/kg/d). (a) Solid tumors in the quercetin treated mice were significantly smaller than those in the control mice. Quercetin significantly reduced (b) tumor volume, and (c) tumor weight, (d) but had no effect on the body weight of mice. Values are means ± SD (mean of triplicate). *p<0.05 denotes a statistically significant difference from untreated controls.
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pone-0047516-g006: Quercetin inhibits tumor growth in a xenograft mouse model.PC-3 cells were injected into 6-week old BALB/cA nude mice (5×106 cells per mouse). After tumors grew to about 100 mm3, mice were treated intraperitoneally with or without quercetin (20 mg/kg/d). (a) Solid tumors in the quercetin treated mice were significantly smaller than those in the control mice. Quercetin significantly reduced (b) tumor volume, and (c) tumor weight, (d) but had no effect on the body weight of mice. Values are means ± SD (mean of triplicate). *p<0.05 denotes a statistically significant difference from untreated controls.

Mentions: We used a xenograft prostate tumor model to investigate the effect of quercetin on tumor growth and angiogenesis. PC-3 prostate cancer cells were injected (5×106 per mouse) into the 6-week-old male BALB/cA nude mice. After the tumors had developed (about 100 mm3), the mice were injected with or without 20 mg/Kg/day quercetin (ip) every day (Fig. 6a). We found that intraperitoneal administration of quercetin significantly suppressed tumor volume (Fig. 6b) and tumor weight (Fig. 6c) but had no effect on the body weight of mice (Fig. 6d). As shown in Figure 6b, tumors in control group increased from 108.31±7.35 to 551.66±61.32 mm3, whereas tumors in quercetin-treated group decreased from 101.77±8.57 to 71.16±2.65 mm3. The average weight of tumors from the control group was 0.242±0.04 gram whereas the average weight in quercetin treated group was only 0.099±0.01 gram, suggesting strong anti-tumor potential of quercetin in xenograft mouse prostate tumor model.


Quercetin inhibits angiogenesis mediated human prostate tumor growth by targeting VEGFR- 2 regulated AKT/mTOR/P70S6K signaling pathways.

Pratheeshkumar P, Budhraja A, Son YO, Wang X, Zhang Z, Ding S, Wang L, Hitron A, Lee JC, Xu M, Chen G, Luo J, Shi X - PLoS ONE (2012)

Quercetin inhibits tumor growth in a xenograft mouse model.PC-3 cells were injected into 6-week old BALB/cA nude mice (5×106 cells per mouse). After tumors grew to about 100 mm3, mice were treated intraperitoneally with or without quercetin (20 mg/kg/d). (a) Solid tumors in the quercetin treated mice were significantly smaller than those in the control mice. Quercetin significantly reduced (b) tumor volume, and (c) tumor weight, (d) but had no effect on the body weight of mice. Values are means ± SD (mean of triplicate). *p<0.05 denotes a statistically significant difference from untreated controls.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3475699&req=5

pone-0047516-g006: Quercetin inhibits tumor growth in a xenograft mouse model.PC-3 cells were injected into 6-week old BALB/cA nude mice (5×106 cells per mouse). After tumors grew to about 100 mm3, mice were treated intraperitoneally with or without quercetin (20 mg/kg/d). (a) Solid tumors in the quercetin treated mice were significantly smaller than those in the control mice. Quercetin significantly reduced (b) tumor volume, and (c) tumor weight, (d) but had no effect on the body weight of mice. Values are means ± SD (mean of triplicate). *p<0.05 denotes a statistically significant difference from untreated controls.
Mentions: We used a xenograft prostate tumor model to investigate the effect of quercetin on tumor growth and angiogenesis. PC-3 prostate cancer cells were injected (5×106 per mouse) into the 6-week-old male BALB/cA nude mice. After the tumors had developed (about 100 mm3), the mice were injected with or without 20 mg/Kg/day quercetin (ip) every day (Fig. 6a). We found that intraperitoneal administration of quercetin significantly suppressed tumor volume (Fig. 6b) and tumor weight (Fig. 6c) but had no effect on the body weight of mice (Fig. 6d). As shown in Figure 6b, tumors in control group increased from 108.31±7.35 to 551.66±61.32 mm3, whereas tumors in quercetin-treated group decreased from 101.77±8.57 to 71.16±2.65 mm3. The average weight of tumors from the control group was 0.242±0.04 gram whereas the average weight in quercetin treated group was only 0.099±0.01 gram, suggesting strong anti-tumor potential of quercetin in xenograft mouse prostate tumor model.

Bottom Line: Quercetin (20 mg/kg/d) significantly reduced the volume and the weight of solid tumors in prostate xenograft mouse model, indicating that quercetin inhibited tumorigenesis by targeting angiogenesis.Furthermore, quercetin reduced the cell viability and induced apoptosis in prostate cancer cells, which were correlated with the downregulation of AKT, mTOR and P70S6K expressions.Collectively the findings in the present study suggest that quercetin inhibits tumor growth and angiogenesis by targeting VEGF-R2 regulated AKT/mTOR/P70S6K signaling pathway, and could be used as a potential drug candidate for cancer therapy.

View Article: PubMed Central - PubMed

Affiliation: Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, Kentucky, United States of America.

ABSTRACT
Angiogenesis is a crucial step in the growth and metastasis of cancers, since it enables the growing tumor to receive oxygen and nutrients. Cancer prevention using natural products has become an integral part of cancer control. We studied the antiangiogenic activity of quercetin using ex vivo, in vivo and in vitro models. Rat aortic ring assay showed that quercetin at non-toxic concentrations significantly inhibited microvessel sprouting and exhibited a significant inhibition in the proliferation, migration, invasion and tube formation of endothelial cells, which are key events in the process of angiogenesis. Most importantly, quercetin treatment inhibited ex vivo angiogenesis as revealed by chicken egg chorioallantoic membrane assay (CAM) and matrigel plug assay. Western blot analysis showed that quercetin suppressed VEGF induced phosphorylation of VEGF receptor 2 and their downstream protein kinases AKT, mTOR, and ribosomal protein S6 kinase in HUVECs. Quercetin (20 mg/kg/d) significantly reduced the volume and the weight of solid tumors in prostate xenograft mouse model, indicating that quercetin inhibited tumorigenesis by targeting angiogenesis. Furthermore, quercetin reduced the cell viability and induced apoptosis in prostate cancer cells, which were correlated with the downregulation of AKT, mTOR and P70S6K expressions. Collectively the findings in the present study suggest that quercetin inhibits tumor growth and angiogenesis by targeting VEGF-R2 regulated AKT/mTOR/P70S6K signaling pathway, and could be used as a potential drug candidate for cancer therapy.

Show MeSH
Related in: MedlinePlus