Effects of Platycodin D on Proliferation, Apoptosis and PI3K/Akt Signal Pathway of Human Glioma U251 Cells

Xu, Chong; Sun, Guibo; Gao, Yuan; Wang, Rui; Sun, Xiaobo

doi:10.3390/molecules191221411

Cited by 40 publications

(37 citation statements)

References 45 publications

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“…High grade glioma is the leading cause of brain cancer-related mortality due to its high invasive ability and malignant proliferation (1,2). Glioma incidence accounts for approximately 40-50% of all intracranial tumors (3). Although current treatment has modestly improved patient survival, patients with gliomas still have a very poor prognosis and low cure rates.…”

Section: Introductionmentioning

confidence: 99%

Dracorhodin perchlorate induces the apoptosis of glioma cells

et al. 2016

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Abstract. Dracorhodin perchlorate (Dp), a synthetic analogue of the antimicrobial anthocyanin red pigment, has recently been shown to induce apoptotic cell death in various types of cancer cells. Yet, the inhibitory effect of Dp on human glioma cells remains uninvestigated. Therefore, in the present study, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry were used to detect cell viability and cell cycle progression in glioma U87MG and T98G cells, respectively. Annexin V-FITC/propidium iodide double staining and JC-1 staining were separately applied to determine cellular apoptosis and mitochondrial membrane potential damage in the cells. The expression levels of associated proteins involved in cell cycle progression and apoptosis were measured by western blotting. The activities of caspase-9/-3 were determined by Caspase-Glo-9/3 assay. The results indicated that Dp treatment significantly inhibited cell proliferation in a dose-and time-dependent manner, and blocked cell cycle progression at the G 1 /S phase in the U87MG and T98G cells via the upregulation of p53 and p21 protein expression, and simultaneous downregulation of Cdc25A, Cdc2 and P-Cdc2 protein expression. Additionally, Dp treatment led to the loss of cellular mitochondrial membrane potential, and the release of cytochrome c, and strongly induced the occurence of apoptosis. Increased expression levels of Bim and Bax protein and the downregulated expression of Bcl-2 protein were observed. Caspase-9/-3 were activated and their activities were elevated after Dp treatment. These findings indicate that Dp inhibits cell proliferation, induces cell cycle arrest and apoptosis in glioma cells, and is a possible candidate for glioma treatment. IntroductionBrain glioma is the most common form of neural malignancy in the nervous system. High grade glioma is the leading cause of brain cancer-related mortality due to its high invasive ability and malignant proliferation (1,2). Glioma incidence accounts for approximately 40-50% of all intracranial tumors (3). Although current treatment has modestly improved patient survival, patients with gliomas still have a very poor prognosis and low cure rates. It was reported that patients with anaplastic astrocytoma have a median survival of 2-3 years, but for those with more aggressive glioblastomas, the median survival is only 12-15 months (4,5). Currently, surgery is considered as an important initial clinical approach for glioma, yet it is difficult to completely remove diffuse tumor cells. Radiotherapy and chemotherapy after initial surgical resection are regarded as an effective therapeutic plan to prevent disease recurrence (6). However, most attempts to increase the efficacy of radiotherapy and chemotherapy are hampered by unacceptable late toxicities (7). In addition, the drug-resistance of tumor cells finally results in the abrogation of the effects of current chemotherapeutic agents (8). Accordingly, to improve the prognosis and quality of life of patients with gliomas, the ...

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Section: Introductionmentioning

confidence: 99%

Dracorhodin perchlorate induces the apoptosis of glioma cells

et al. 2016

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“…In this study, we provided evidence that platycodin D had the ability to cause growth suppression and apoptosis in OSCC cells. The antiproliferative activity of platycodin D has also been observed in other malignancies such as breast cancer, glioma, and prostate cancer . It has been reported that platycodin D promotes caspase‐mediated apoptosis in AGS human gastric cancer cells .…”

Section: Discussionmentioning

confidence: 99%

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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“…PGD is classified as a triterpenoid saponin and is one of the main chemical components of P. grandiflorum. PGD has a very similar structure to Platycodin D, a well known anticancer agent (11)(12)(13)(14). Based on this relationship, we hypothesized that PGD would also have anticancer effects.…”

Section: Introductionmentioning

confidence: 99%

Polygalacin D induces apoptosis and cell cycle arrest via the PI3K/Akt pathway in non-small cell lung cancer

et al. 2018

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Polygalacin D (PGD) is a bioactive compound isolated from Platycodon grandiflorum (Jacq.) and it has a similar structure to platycodin D, which is a well known anticancer agent. In the present study, we investigated the anti-proliferative effects of PGD using NSCLC cell lines. We evaluated the effects of PGD on proliferation, apoptosis and cell cycle arrest in A549 and H460 cells. PGD significantly induced apoptosis and nuclear condensation in both cell lines. Furthermore, PGD upregulated the cleavage of apoptotic proteins such as caspase-3, -9 and PARP. Additionally, treatment with PGD suppressed the expression of the IAP family of proteins including survivin, cIAP-1 and cIAP-2. Furthermore, PGD induced G0/G1-phase arrest in both cell lines. After treatment with PGD, the expression of TIMP-1, CDK2, cyclin A and cyclin E was reduced at the protein level. In addition, PGD blocked the PI3K/Akt pathway by inhibiting the phosphorylation of GSK3β, Akt and the expression of PI3K. Our results indicated that the anti-proliferative properties of PGD may result from the regulation of the PI3K/Akt pathway, which plays a critical role in cell survival and growth.

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Effects of Platycodin D on Proliferation, Apoptosis and PI3K/Akt Signal Pathway of Human Glioma U251 Cells

Cited by 40 publications

References 45 publications

Dracorhodin perchlorate induces the apoptosis of glioma cells

Dracorhodin perchlorate induces the apoptosis of glioma cells

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

Polygalacin D induces apoptosis and cell cycle arrest via the PI3K/Akt pathway in non-small cell lung cancer

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