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Platycodin D Induces Tumor Growth Arrest by Activating FOXO3a Expression in Prostate Cancer in vitro and in vivo

View Article: PubMed Central - PubMed

ABSTRACT

Platycodin D (PD), a major saponin derived from Platycodin grandiflorum, exerted cytotoxicity against prostate cancer cell lines (PC3, DU145 and LNCaP cells) with IC50 values in the range of 11.17 to 26.13μmol/L, whereas RWPE-1cells (a non-malignant human prostate epithelial cell line) were not significantly affected. A further study in these cell lines showed that PD could potently affect cell proliferation (indicated by the bromodeoxyuridine assay), induce cell apoptosis (determined by Annexin V-FITC flow cytometry) and cause cell cycle arrest (indicated by PI staining). After being treated with PD for 48 hours, DU145 and LNCaP cells were arrested in the G0 /G1 phase, and PC3 cells were arrested in the G2/M phase. A Western blotting analysis indicated that PD increased the expression of the FOXO3a transcription factor, decreased the expression of p-FOXO3a and MDM2 and increased the expression of FOXO-responsive genes, p21 and p27. MDM2 silencing (transiently by siRNA-MDM2) increased the PD-induced FOXO3a protein expression, while MDM2 overexpression (in cells transiently transfected with a pcDNA3-MDM2 plasmid) decreased the PD-induced expression of the FOXO3a protein. Moreover, PD dose-dependently inhibited the growth of PC3 xenograft tumors in BALB/c nude mice. A Western blotting analysis of the excised xenograft tumors indicated that similar changes in protein expression also occurred in vivo. These results suggest that PD exhibits significant activity against prostate cancer in vitro and in vivo. The FOXO3a transcription factor appears to be involved in the activity of PD. Together, all of these findings provide a basis for the future development of this agent for human prostate cancer therapy.

No MeSH data available.


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The in vivo effects of PD in nude mice bearing PC3 xenograft tumors. PD was injected intraperitoneally (i.p.) at doses of 1 mg/kg/d and 2.5 mg/kg/d, 5 d/wk for 24 days. A. Animals were monitored for changes in body weight every three days as an indicator of toxicity. B. At the end of the experiment, representative tumors were removed and photographed. C. The tumors were measured every three days to assess their growth.
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Figure 6: The in vivo effects of PD in nude mice bearing PC3 xenograft tumors. PD was injected intraperitoneally (i.p.) at doses of 1 mg/kg/d and 2.5 mg/kg/d, 5 d/wk for 24 days. A. Animals were monitored for changes in body weight every three days as an indicator of toxicity. B. At the end of the experiment, representative tumors were removed and photographed. C. The tumors were measured every three days to assess their growth.


Platycodin D Induces Tumor Growth Arrest by Activating FOXO3a Expression in Prostate Cancer in vitro and in vivo
The in vivo effects of PD in nude mice bearing PC3 xenograft tumors. PD was injected intraperitoneally (i.p.) at doses of 1 mg/kg/d and 2.5 mg/kg/d, 5 d/wk for 24 days. A. Animals were monitored for changes in body weight every three days as an indicator of toxicity. B. At the end of the experiment, representative tumors were removed and photographed. C. The tumors were measured every three days to assess their growth.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4997962&req=5

Figure 6: The in vivo effects of PD in nude mice bearing PC3 xenograft tumors. PD was injected intraperitoneally (i.p.) at doses of 1 mg/kg/d and 2.5 mg/kg/d, 5 d/wk for 24 days. A. Animals were monitored for changes in body weight every three days as an indicator of toxicity. B. At the end of the experiment, representative tumors were removed and photographed. C. The tumors were measured every three days to assess their growth.

View Article: PubMed Central - PubMed

ABSTRACT

Platycodin D (PD), a major saponin derived from Platycodin grandiflorum, exerted cytotoxicity against prostate cancer cell lines (PC3, DU145 and LNCaP cells) with IC50 values in the range of 11.17 to 26.13μmol/L, whereas RWPE-1cells (a non-malignant human prostate epithelial cell line) were not significantly affected. A further study in these cell lines showed that PD could potently affect cell proliferation (indicated by the bromodeoxyuridine assay), induce cell apoptosis (determined by Annexin V-FITC flow cytometry) and cause cell cycle arrest (indicated by PI staining). After being treated with PD for 48 hours, DU145 and LNCaP cells were arrested in the G0 /G1 phase, and PC3 cells were arrested in the G2/M phase. A Western blotting analysis indicated that PD increased the expression of the FOXO3a transcription factor, decreased the expression of p-FOXO3a and MDM2 and increased the expression of FOXO-responsive genes, p21 and p27. MDM2 silencing (transiently by siRNA-MDM2) increased the PD-induced FOXO3a protein expression, while MDM2 overexpression (in cells transiently transfected with a pcDNA3-MDM2 plasmid) decreased the PD-induced expression of the FOXO3a protein. Moreover, PD dose-dependently inhibited the growth of PC3 xenograft tumors in BALB/c nude mice. A Western blotting analysis of the excised xenograft tumors indicated that similar changes in protein expression also occurred in vivo. These results suggest that PD exhibits significant activity against prostate cancer in vitro and in vivo. The FOXO3a transcription factor appears to be involved in the activity of PD. Together, all of these findings provide a basis for the future development of this agent for human prostate cancer therapy.

No MeSH data available.


Related in: MedlinePlus