Polyphyllin D, a steroidal saponin from Paris polyphylla, inhibits endothelial cell functions in vitro and angiogenesis in zebrafish embryos in vivo

Chan, Judy Yuet-Wa; Koon, J.C.M.; Liu, Xiaozhuo; Detmar, Michael; Yu, Bo; Kong, Siu‐Kai; Fung, Kwok‐Pui

doi:10.1016/j.jep.2011.04.021

Cited by 75 publications

(56 citation statements)

References 30 publications

(35 reference statements)

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“…PSI has been approved for cancer therapy due to its potential involvement in the suppression of tumor growth (13)(14)(15)(16). The inhibitory effects of PSI were associated with increased levels of pro-apoptotic Bax, cytochrome c, active caspase-9 and active caspase-3.…”

Section: Discussionmentioning

confidence: 99%

“…Five Paris saponins have been identified: Paris saponin I (PSI), also known as polyphyllin D (8)(9)(10)(11)(12), Paris saponin V (PSV), Paris saponin VI (PSVI), Paris saponin VII (PSVII) and Paris saponin H (PSH). As the active ingredient, Paris saponin I (PSI) is important in the treatment of cancer due to its anti-tumor activity, cytotoxic effects and anti-angiogenic activity (13)(14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of cell proliferation by mild hyperthermia at 43°C with Paris Saponin I in the lung adenocarcinoma cell line PC-9

Zhao

Jiang

et al. 2014

Molecular Medicine Reports

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Abstract. Rhizoma paridis is widely used for cancer therapy due to its potential involvement in the suppression of tumor growth. However, at present there is no clear explanation for the mechanism underlying the inhibitory effects of Rhizoma paridis combined with hyperthermia on tumor growth. The aim of the present study was to evaluate the effects of Paris saponin I (PSI) combined with hyperthermia on a variety of non-small cell lung cancer (NSCLC) cell lines. An MTT assay was used to determine the levels of growth inhibition. The cell cycle was analyzed using flow cytometry and cell apoptosis was analyzed with Annexin V/propidium iodide staining and the Hoechst assay. The morphology of cells during apoptosis was determined using a transmission electron microscope. The expression levels of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax) and caspase-3 proteins were detected using western blotting. The inhibition rates significantly increased with PSI in combination with hyperthermia at 43˚C. PSI with hyperthermia at 43˚C caused G2/M phase arrest and significantly induced apoptosis. The expression level of Bcl-2 decreased, while Bax expression increased following treatment with PSI with hyperthermia at 43˚C. In addition, the protein expression of caspase-3 was significantly enhanced. PSI combined with hyperthermia is a potent antitumor treatment through the inhibition of proliferation of NSCLC cells and may be developed as a new antitumor therapy. PSI combined with hyperthermia significantly induced apoptosis through a multi regulatory process involving G2/M arrest and regulation of Bax, Bcl-2 and caspase-3 expression, resulting in cell death and tumor inhibition.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Inhibition of cell proliferation by mild hyperthermia at 43°C with Paris Saponin I in the lung adenocarcinoma cell line PC-9

Zhao

Jiang

et al. 2014

Molecular Medicine Reports

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“…Furthermore, Paris saponin II significantly inhibited tumor growth by 70% in the human SKOV3 ovarian cancer xenograft model (17), and Paris saponin H showed a marked cytotoxic activity on A549 cells with an IC 50 value of 1.53±0.08 µg/ml (18). Paris saponin D has been shown to overcome drug resistance in R-HepG2 cells, elicit programmed cell death via mitochondrial dysfunction, inhibit endothelial cell functions in vitro and inhibit angiogenesis in zebrafish embryos in vivo (19,20). Preclinical studies have made Paris saponins emerge as promising anti-cancer agents.…”

Section: Introductionmentioning

confidence: 99%

Paris saponin I induces apoptosis via increasing the Bax/Bcl-2 ratio and caspase-3 expression in gefitinib-resistant non-small cell lung cancer in vitro and in vivo

Jiang

Zhao

et al. 2014

Molecular Medicine Reports

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Abstract. Polyphyllins, a major component of Rhizoma paridis, have been extensively used in non-small cell lung cancer (NSCLC). The aim of the present study was to evaluate the effects of Paris saponin I (PSI) on a panel of gefitinib-resistant NSCLC cell lines and its inhibition of tumor growth in a nude mouse model. The MTT assay was used to assess growth inhibition. The cell cycle was analyzed using flow cytometry and apoptosis was assessed using Annexin V/propidium iodide staining. The morphology of the apoptotic cells was determined by transmission electron microscopy. The protein expression levels of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax) and caspase-3 were detected using western blot analysis. In addition, the glucose metabolism in tumor-bearing mice was evaluated using 18 F-fludeoxyglucose (FDG) micro-positron emission tomography imaging. The PSI-induced growth inhibition rate was observed to significantly increase in a time-and dose-dependent manner. Furthermore, PSI induced significant G2/M-phase arrest and apoptosis. The expression levels of Bcl-2 decreased, while those of Bax and caspase-3 increased following PSI treatment.18 F-FDG-uptake in the PSI treatment groups was significantly decreased compared with that in the control group in vivo. In conclusion, PSI is a potent antitumor agent that acts by inhibiting the proliferation of gefitinib-resistant cells, and has potential as a candidate for a natural drug for gefitinib-resistant therapy. PSI-induced apoptosis, which occurred via multiple pathways, including G2/M-phase arrest and upregulation of the Bax/Bcl-2 ratio and caspase-3 expression, ultimately led to cell death and tumor inhibition.

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“…This compound displayed in vitro angiogenesis inhibition, by suppressing cell proliferation, migration and tube formation; and in vivo angiogenesis inhibition by the ability to impair intersegmental vessels formation in zebrafish embryos [161].…”

Section: Antiangiogenic Potential Of Other Natural Compoundsmentioning

confidence: 99%

Antiangiogenic compounds: well-established drugs versus emerging natural molecules

et al. 2018

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a b s t r a c tAngiogenesis is the natural and physiologic process of growing blood vessels from pre-existing ones. Pathological angiogenesis occurs when the precise balance of all the molecular pathways that regulate angiogenesis is disrupted, and this process is a critical step in many diseases, including cancer. A limited number of antiangiogenic synthetic drugs have been developed. However, due to toxicity and side effects issues, the search for alternative to existing drugs is ongoing. In this sense, natural molecules obtained from plants or macrofungi, have demonstrated extraordinary potential in the treatment of angiogenesisrelated pathologies, specially taking into consideration its absence or very low toxicity, when compared to synthetic drugs. Using natural compounds as potential angiogenesis modulators is thus a promising field of research, supporting the creation of novel therapies able to reduce the use of drugs and associated side effects. In this review, the current status of antiangiogenic drugs and the wide variety of natural extracts and molecules with antiangiogenic capacities, as well as the angiogenesis molecular pathways and therapeutic targets, are presented. Finally, the challenges that need to be overcome in order to increase the use of natural compounds for clinical purposes are discussed.

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Polyphyllin D, a steroidal saponin from Paris polyphylla, inhibits endothelial cell functions in vitro and angiogenesis in zebrafish embryos in vivo

Cited by 75 publications

References 30 publications

Inhibition of cell proliferation by mild hyperthermia at 43°C with Paris Saponin I in the lung adenocarcinoma cell line PC-9

Inhibition of cell proliferation by mild hyperthermia at 43°C with Paris Saponin I in the lung adenocarcinoma cell line PC-9

Paris saponin I induces apoptosis via increasing the Bax/Bcl-2 ratio and caspase-3 expression in gefitinib-resistant non-small cell lung cancer in vitro and in vivo

Antiangiogenic compounds: well-established drugs versus emerging natural molecules

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