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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.


Related in: MedlinePlus

PD induces concentration-dependent apoptosis in prostate cancer cells. The induction of apoptosis in PC3 cells (A), LNCaP cells (B) and DU145 cells (C) treated with various concentrations of PD for 48 hr. All assays were performed in triplicate. The apoptosis index was calculated compared to that in untreated control cells. (*, p<0.05 versus the control).
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Figure 2: PD induces concentration-dependent apoptosis in prostate cancer cells. The induction of apoptosis in PC3 cells (A), LNCaP cells (B) and DU145 cells (C) treated with various concentrations of PD for 48 hr. All assays were performed in triplicate. The apoptosis index was calculated compared to that in untreated control cells. (*, p<0.05 versus the control).

Mentions: We also examined whether PD induced apoptosis in prostate cancer cells. As illustrated in Fig. 2, the examined prostate cancer cell lines exhibited a significant increase (p<0.05) in apoptosis following exposure to a 10 μM or higher concentration of the compound. In the PC3, LNCaP and DU145 cells (Fig. 3), 20 μM PD increased the cells death by more 15.0%, 12.7% and 18.1%, respectively, compared to that in the DMSO-treated control cells.


Platycodin D Induces Tumor Growth Arrest by Activating FOXO3a Expression in Prostate Cancer in vitro and in vivo
PD induces concentration-dependent apoptosis in prostate cancer cells. The induction of apoptosis in PC3 cells (A), LNCaP cells (B) and DU145 cells (C) treated with various concentrations of PD for 48 hr. All assays were performed in triplicate. The apoptosis index was calculated compared to that in untreated control cells. (*, p<0.05 versus the control).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: PD induces concentration-dependent apoptosis in prostate cancer cells. The induction of apoptosis in PC3 cells (A), LNCaP cells (B) and DU145 cells (C) treated with various concentrations of PD for 48 hr. All assays were performed in triplicate. The apoptosis index was calculated compared to that in untreated control cells. (*, p<0.05 versus the control).
Mentions: We also examined whether PD induced apoptosis in prostate cancer cells. As illustrated in Fig. 2, the examined prostate cancer cell lines exhibited a significant increase (p<0.05) in apoptosis following exposure to a 10 μM or higher concentration of the compound. In the PC3, LNCaP and DU145 cells (Fig. 3), 20 μM PD increased the cells death by more 15.0%, 12.7% and 18.1%, respectively, compared to that in the DMSO-treated control cells.

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 26.13&mu;mol/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