Polyphyllin D

Polyphyllin D induces apoptosis in K562/A02 cells through G2/M phase arrest.[Pubmed: 24325805]

J Pharm Pharmacol. 2014 May;66(5):713-21.

The effect of Polyphyllin D on inducing cell death of the K562/A02 human leukaemia drug-resistant cells in vitro was examined.
METHODS AND RESULTS:
The effect of Polyphyllin D on K562/A02 cells were analysed by studying their cytotoxicity, apoptosis, cell cycle distribution, caspase-3 activity and disruption of mitochondrial membrane potential (MMP). Polyphyllin D, a small molecular monomer extracted from rhizoma of Paris polyphyllin, exhibited strong anticancer activity in a previous study. Our results demonstrate that Polyphyllin D exerts a growth inhibitory effect by arresting cells at G2/M phase and by the induction of apoptosis in K562/A02 human leukaemia drug-resistant cells, G2/M phase arrest was found to be associated with up-regulation of p21 and down-regulation of cyclin B1 and cyclin-dependent protein kinase 1. Polyphyllin D-induced apoptosis via the mitochondrial apoptotic pathway as evidenced by decreased Bcl-2 expression levels, disruption of MMP and increased Bax, cytochrome C and cleaved-caspase-3 levels.
CONCLUSIONS:
These data suggest that Polyphyllin D has a potential as a potent therapeutic agent for chronic myeloid leukaemia.

Polyphyllin D induces apoptosis in human erythrocytes through Ca²⁺ rise and membrane permeabilization.[Pubmed: 22349056]

Arch Toxicol. 2012 May;86(5):741-52.

Polyphyllin D (PD) is a potent anticancer agent isolated from a traditional medicinal herb Paris polyphylla that has been used in China for many years to treat cancer. Polyphyllin D is not a substrate of p-glycoprotein, and it can bypass the multi-drug resistance in cancer cell line R-HepG2. However, the effect of Polyphyllin D on the induction of cell death in human erythrocytes remains unknown. Given that Polyphyllin D is a small molecule that can depolarize the mitochondrial membrane potential and release apoptosis-inducing factor (AIF) in isolated mitochondria, we hypothesized that the apoptogenic effect of Polyphyllin D in human erythrocytes devoid of mitochondria would be minimal. This study therefore tried to evaluate the in vitro effect of Polyphyllin D on hemolysis and apoptosis in human erythrocytes.
METHODS AND RESULTS:
Apoptosis in human red blood cells (RBCs), also known as eryptosis or erythroptosis, after Polyphyllin D treatment was determined by flow cytometry and confocal microscopy for the phosphatidyl-serine externalization and other apoptosis feature events. False to our prediction, Polyphyllin D caused hemolysis and eryptosis/erythroptosis in human RBCs. Mechanistically, elevation in the cytosolic Ca²⁺ ion level seems to be a key but not the only mediator in the Polyphyllin D-mediated eryptosis/erythroptosis because depletion of the external Ca²⁺ could not eliminate the Polyphyllin D effect. Also, Polyphyllin D was able to permeabilize the membrane of RBC ghosts in a way similar to digitonin.
CONCLUSIONS:
Taken together, we report here for the first time the toxicity of Polyphyllin D in human RBCs as well as its underlying mechanism for the hemolysis and eryptosis/erythroptosis.

Polyphyllin D, a steroidal saponin from Paris polyphylla, inhibits endothelial cell functions in vitro and angiogenesis in zebrafish embryos in vivo.[Pubmed: 21658438]

J Ethnopharmacol. 2011 Sep 1;137(1):64-9.

Angiogenesis, the process of blood vessel formation, is critical to tumour growth. The importance of angiogenesis in tumour development has lead to the development of anti-angiogenic strategies to inhibit tumour growth. In this study, Polyphyllin D (PD), an active component in Chinese herb, Paris polyphylla, was evaluated for its potential anti-angiogenic effects.
METHODS AND RESULTS:
The inhibitory effects of Polyphyllin D on three important processes involved in angiogenesis, i.e. proliferation, migration and differentiation were examined using human microvascular endothelial cell line HMEC-1 by MTT assay, scratch assay and tube formation assay, respectively. Using zebrafish embryos as an animal model of angiogenesis, the anti-angiogenic effect of Polyphyllin D was further verified in vivo. Polyphyllin D suppressed the growth of HMEC-1 cells at 0.1-0.4 μM without toxic effects. At 0.3 μM and 0.4 μM, Polyphyllin D significantly inhibited endothelial cell migration and capillary tube formation. About 70% of the zebrafish embryos showed defects in intersegmental vessel formation upon treatment with Polyphyllin D at concentrations of 0.156 μM and 0.313 μM.
CONCLUSIONS:
The anti-angiogenic effects of Polyphyllin D have been explored in the study which implied a potential therapeutic development of Polyphyllin D in cancer treatment.

Polyphyllin D induces apoptosis in U87 human glioma cells through the c-Jun NH2-terminal kinase pathway.[Pubmed: 25045920]

J Med Food. 2014 Sep;17(9):1036-42.

Polyphyllin D (PD), an active component from a traditional medicinal herb Paris polyphylla, which has long been used for the treatment of cancer in Asian countries, has been found to hold significant antitumor activity in vivo or in vitro. However, there were few reports on the effects and underlying mechanism of Polyphyllin D on apoptosis in U87 human glioma cells.
METHODS AND RESULTS:
The present study was conducted to evaluate apoptotic induction of Polyphyllin D in U87 human glioma cells, and explore its underlying pathway. U87 glioma cells were cultured and treated with varied concentrations of Polyphyllin D (from 10(-8) to 10(-4) M). The inhibition of U87 glioma cell proliferation by Polyphyllin D was assessed by MTT assay. The apoptosis of U87 glioma cells was detected by flow cytometry, and western blot analysis was used to examine human B-cell leukemia/lymphoma 2 (Bcl-2), human Bcl-2 associated X protein (Bax), caspase-3, total-c-jun NH2-terminal kinase (t-JNK), and phosphorylation-JNK (p-JNK) protein expression in U87 human glioma cells. The treatment with Polyphyllin D for 24 h significantly inhibited the proliferation of U87 human glioma cells in a concentration-dependent manner. Polyphyllin D increased apoptosis and significantly upregulated the expression of Bax, caspase-3, and p-JNK associated with apoptosis, but downregulated antiapoptotic Bcl-2 expression in U87 human glioma cells.
CONCLUSIONS:
Our data provided evidences that Polyphyllin D induces apoptosis in U87 human glioma cells. This effect might be associated with the JNK pathway.

Polyphyllin D exerts potent anti-tumour effects on Lewis cancer cells under hypoxic conditions.[Pubmed: 19589245]

J Int Med Res. 2009 May-Jun;37(3):631-40.

Paris polyphylla has been used to treat cancer in China for many years and components of the plant, such as Polyphyllin D, may have potent antiproliferative effects in vitro.
METHODS AND RESULTS:
To investigate the potential antitumour effects of Polyphyllin D on cancer cells under hypoxia, Lewis lung cancer cells and mouse tracheal epithelial cells were cultured with or without Polyphyllin D under normoxic and hypoxic conditions. Proliferation and apoptosis of cells were assayed. Real-time reverse transcription-polymerase chain reaction was used to quantify the expression of hypoxia-inducible factor 1 alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) mRNA. Polyphyllin D decreased cell proliferation, increased apoptosis and inhibited expression of HIF-1alpha and VEGF mRNAs in Lewis cells. These effects were greater under hypoxic than normoxic conditions. Polyphyllin D did not show a cytotoxic effect in non-tumour cells (mouse skin fibroblasts and tracheal epithelial cells).
CONCLUSIONS:
These results suggest that Polyphyllin D potentially has anticancer effects in vitro under hypoxia.