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

Zhou, Rui; Lu, Zongliang; Li, Kai; Guo, Jing; Liu, Jie; Zhou, Yong; Yang, Jian; Mi, Mantian; Xu, Hongxia

doi:10.2174/1568009614666141128104642

Cited by 31 publications

(44 citation statements)

References 36 publications

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“…The IC 50 value of PD for inhibiting cell growth was less than 10 µM, and treatment of cells with 20 µM PD decreased the proliferation index to 34±0.05% of the rate observed in the control group. These anti-proliferative effects were consistent with those reported in previous studies (10,12,15,26). Furthermore, we detected the expression of Ki67 in MDA-MB-231 cells, which is a classic marker of cell proliferation.…”

Section: Discussionsupporting

confidence: 92%

“…It is interesting that PD may have different effects on the cell cycle in different cell lines. As we reported previously, PD induced cell cycle arrest in the G0/G1 phase in the DU145 and LnCaP prostate cancer cell lines, but induced arrest in the G2/M phase in the PC3 prostate cancer cell line (12).…”

Section: Discussionsupporting

confidence: 83%

“…As the most abundant triterpenoid saponin derived from the roots of Platycodin grandiflorum, Platycodin D (PD), has been reported to show a wide range of health benefits, such as anti-atherosclerotic (4), anti-inflammatory (5,6), hypocholesterolemic and anti-obesity effects (7). Previous studies have shown that PD has obvious anticancer activity against different human malignant cancer cells both in vitro (10,11,13,14,16,17) and in vivo (9,12,15).…”

Section: Discussionmentioning

confidence: 99%

“…The pcDNA3-Flag-MDM2 plasmid was provided by Dr Ruiwen Zhang, Texas Tech University health Sciences Center (Amarillo, TX, USA). MDA-MB-231 cells were transfected with 3 µg pcDNA3-Flag-MDM2 plasmid for 5-7 h and were then treated with PD (20 µM) for 24 h. The procedure was carried out as previously described (12). Western blot analysis was performed to assess the expression of various proteins.…”

Section: Cell Cycle Analysismentioning

confidence: 99%

“…Platycodin D (PD), a triterpenoid saponin derived from the roots of Platycodin grandiflorum, has been reported to possess a wide rangeof health benefits, such as anti-atherosclerotic (4), anti-inflammatory (5,6), hypocholesterolemic, and anti-obesity effects (7), as well as spermicidal and contraceptive activity (8). Among the various health benefits of PD, anticancer effects have been noted in several cancer cell lines, including lung cancer cells (9), hepatocellular carcinoma cells (10), gastric cancer cells (11), prostate cancer cells (12), and leukemia cells (13,14). PD has also been reported to inhibit the viability of human breast cancer cells in vitro (15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

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Platycodin D, a metabolite of Platycodin grandiflorum, inhibits highly metastatic MDA-MB-231 breast cancer growth in vitro and in vivo by targeting the MDM2 oncogene

Kong

Wang

et al. 2016

Oncology Reports

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Abstract. The objective of the present study was to explore the in vitro and in vivo anticancer effects of Platycodin D (PD), derived from Platycodin grandiflorum, on highly metastatic MDA-MB-231 breast cancer cells. Using the MTT assay, we found that PD inhibited MDA-MB-231 cell growth in a concentration-dependent manner, with an IC 50 value of 7.77±1.86 µM. Further studies showed that PD had antiproliferative effects and induced cell cycle arrest in the G0/G1 phase. To explore the detailed mechanism(s) by which PD suppressed MDA-MB-231 cell growth, western blot analyses were used to detect the expression levels of proteins related to cell proliferation and survival. The data showed that PD decreased the expression of proteins related to the G0/G1 phases, downregulated the protein expression of MDM2, MDMX, and mutant p53, and increased the expression levels of p21 and p27 in vitro. We verified the effects of PD on the expression of MDM2, MDMX, mutant p53, p21 and p27 using a pcDNA3-Flag-MDM2 plasmid and MDM2 siRNA transfection, and found that PD inhibited MDA-MB-231 cell viability by targeting MDM2 and mutant p53. Compared with the corresponding parental cells, the cells with siRNA-MDM2 transfection had a greater decrease in cell viability and proliferation, while those with pcDNA3-MDM2 plasmid transfection did not show any increase in the effects of PD. We also established a MDA-MB-231 xenograft model in BALB/c nude mice, and found that PD significantly inhibited the growth of MDA-MB-231 xenograft tumors in these mice. The expression levels of various proteins in the tumor tissue exhibited changes similar to those observed in vitro. These findings indicate that PD exerted in vitro and in vivo anticancer effects against MDA-MB-231 breast cancer cells, that PD is a potential MDM2/MDMX inhibitor, and that the anticancer effects of PD were likely associated with its inhibition of these proteins. Our observations help to identify a mechanism by which PD functions as an anti-breast cancer agent. IntroductionBreast cancer is the most frequently diagnosed malignancy and the leading cause of cancer death among females worldwide, accounting for 25% of all cancer cases and 15% of the total cancer deaths in 2012 (1). According to the American Cancer Society, about 231,840 new cases of invasive breast cancer and approximately 60,290 new cases of carcinoma in situ would occur in the US in 2015 (2). To relieve the huge burden of cancer therapy and promote women's health, there is an urgent need to discover new drugs to treat breast cancer.Natural products, such as thymoquinone, wogonin, naphtho, and quercetin, have been shown to possess different anticancer functions, such as the induction of cell cycle arrest, suppression of tumor angiogenesis, and inhibition of cell migration or invasion (3). Platycodin D (PD), a triterpenoid saponin derived from the roots of Platycodin grandiflorum, has been reported to possess a wide rangeof health benefits, such as anti-atherosclerotic (4), anti-inflammatory (5,6), hypocholesterolemic, ...

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Cell Cycle Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Platycodin D, a metabolite of Platycodin grandiflorum, inhibits highly metastatic MDA-MB-231 breast cancer growth in vitro and in vivo by targeting the MDM2 oncogene

Kong

Wang

et al. 2016

Oncology Reports

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Platycodin D, a triterpenoid saponin from Platycodon grandiflorum , suppresses the growth and invasion of human oral squamous cell carcinoma cells via the NF-κB pathway

Zhang

Zhao

Zheng

et al. 2017

J Biochem Mol Toxicol

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This work was undertaken to explore the effects of platycodin D, a triterpenoid saponin from Platycodon grandiflorum, on the growth and invasiveness of human oral squamous cell carcinoma (OSCC). Platycodin D caused a significant, concentration-dependent inhibition of cell viability and induced significant apoptosis in OSCC cells. Moreover, platycodin D significantly inhibited OSCC cell invasion. At the molecular level, platycodin D increased the amounts of IκBα protein and reduced the expression of phosphorylated NF-κB p65, MMP-2, and MMP-9. Ectopic expression of constitutively active NF-κB p65 prevented platycodin D-mediated induction of apoptosis and suppression of invasion in OSCC cells. In vivo studies confirmed that platycodin D retarded the growth of subcutaneous SCC-4 xenograft tumors and reduced phosphorylation of NF-κB p65. Altogether, platycodin D shows inhibitory activity on OSCC growth and invasion through inactivation of the NF-κB pathway and might provide therapeutic benefits in the treatment of OSCC.

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Evaluation of the anticancer and anti‐metastasis effects of novel synthetic sodium channel blockers in prostate cancer cells in vitro and in vivo

Wang

et al. 2018

The Prostate

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Background: Voltage-gated sodium channels (VGSCs) are involved in several cellular processes related to cancer cell growth and metastasis, including adhesion, proliferation, apoptosis, migration, and invasion. We here in investigated the effects of S0154 and S0161, two novel synthetic sodium channel blockers (SCBs), on human prostate cancer cells (PC3, DU145, and LnCaP) and a prostate cancer xenograft model. Methods:The MTT assay was used to assess the anticancer effects of SCBs in PC3, DU145, and LnCaP cells. Sodium indicator and glucose uptake assays were used to determine the effects of S0154 and S0161 in PC3 cells. The impact of these SCBs on the proliferation, cell cycle, apoptosis, migration, and invasion of PC3 cells were determined using a CFDA-SE cell proliferation assay, cell cycle assay, annexin V-FITC apoptosis assay, transwell cell invasion assay, and wound-healing assay, respectively.The protein expression levels of Nav1.6, Nav1.7, CDK1, cyclin B1, MMP2, MMP9 in PC3 cells were analysis by Western blotting. The in vivo anticancer activity was evaluated using a PC3 xenograft model in nude mice.Results: S0154 and S0161 both showed anticancer and anti-metastatic effects against prostate cancer cells and significantly inhibited cell viability, with IC 50 values in the range of 10.51-26.60 μmol/L (S0154) and 5.07-11.92 μmol/L (S0161). Both compounds also increased the intracellular level of sodium, inhibited the protein expression of two α subunits of VGSCs (Nav1.6 and Nav1.7), and caused G2/M phase cell cycle arrest, with no or minor effects on cell apoptosis. Concentrations of 5 and 10 μmol/L of S0154 and S0161 significantly decreased the glucose uptake of PC3 cells. The compounds also inhibited the proliferation of PC3 cells and decreased their invasion in transwell assays. Furthermore, S0161 exerted antitumor activity in an in Jiajia Wang and Zongliang Lu contributed equally to this work. wileyonlinelibrary.com/journal/pros The Prostate. 2019;79:62-72.

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

Cited by 31 publications

References 36 publications

Platycodin D, a metabolite of Platycodin grandiflorum, inhibits highly metastatic MDA-MB-231 breast cancer growth in vitro and in vivo by targeting the MDM2 oncogene

Platycodin D, a metabolite of Platycodin grandiflorum, inhibits highly metastatic MDA-MB-231 breast cancer growth in vitro and in vivo by targeting the MDM2 oncogene

Platycodin D, a triterpenoid saponin from Platycodon grandiflorum , suppresses the growth and invasion of human oral squamous cell carcinoma cells via the NF-κB pathway

Evaluation of the anticancer and anti‐metastasis effects of novel synthetic sodium channel blockers in prostate cancer cells in vitro and in vivo

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