Polyphyllin D, a steroidal saponin in Paris polyphylla, induces apoptosis and necroptosis cell death of neuroblastoma cells

Watanabe, Susumu; Suzuki, Tatuya; Hara, Fujio; Yasui, Toshihiro; Uga, Naoko; Naoe, Atuki

doi:10.1007/s00383-017-4069-4

Cited by 28 publications

(30 citation statements)

References 20 publications

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“…Polyphyllin D induced apoptosis and necrosis in cells in a caspase-dependent manner as we reported previously [11]. Arctigenin also induced apoptosis in lung cancer, breast cancer, gallbladder cancer, hepatocellular carcinoma, and colorectal cancer cells [5][6][7][8][9][10].…”

Section: Resultsmentioning

confidence: 76%

“…Previously, we treated cells from a neuroblastoma cell line with polyphyllin D and observed its antitumor effects. The results of our experiment indicated that necroptosis occurred in a cell line with the MYCN gene, while apoptosis occurred in a cell line lacking the MYCN gene [11]. Although the pathways mediating the antitumor effect of arctigenin are different in various tumors, apoptosis induction occurs in all tumors [5][6][7][8][9][10].…”

Section: Discussionmentioning

confidence: 99%

“…We examined the anti-tumor effects of arctigenin 1 Pediatric Surgery Department, Fujita Health University, Toyoake, Japan in the hepatoblastoma cell line HUH-6 clone 5 (hereinafter, referred to as HUH-6). We previously reported that polyphyllin D exhibits anti-tumor effects in a human neuroblastoma cell line [11]. We tested the anti-tumor effects of arctigenin using the same methods as described in our previous study.…”

Section: Introductionmentioning

confidence: 99%

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Arctigenin induces apoptosis in human hepatoblastoma cells

et al. 2019

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Purpose Arctigenin has been shown to have anti-tumor effects in various types of cancers. This study was conducted to verify these effects in the human-derived hepatoblastoma cell line, HUH-6 clone 5 (hereinafter, HUH-6). Methods Arctigenin was added to cultured HUH-6 cells, and cellular activity was evaluated by MTS assay. To determine the relationship between reduced cellular activity and apoptosis, we measured the activities of caspase 3/7, 8, and 9 and conducted flow cytometry with Annexin V/PI staining. Results The MTS assay revealed that cellular activity decreased after arctigenin treatment in a concentration-dependent manner (IC 50 = 4 µM). To investigate apoptosis induction, activity assays of caspase 3/7, 8, and 9 were performed. While caspase 3/7 and 8 exhibited high activity, caspase 9 showed no activity. Thus, apoptosis induction may have involved the action of tumor necrosis factor receptor 1 (TNFR1). Flow cytometry conducted with Annexin V/PI staining revealed the occurrence of early apoptosis. Conclusion We found that arctigenin has anti-tumor effects in HUH-6 cells in a concentration-dependent manner. Arctigenin may have exerted its anti-tumor effect by inducing apoptosis via TNFR1, which recruits Complex IIa to activate caspase 8 and 3/7. These results may be useful for developing therapeutic agents for hepatoblastoma.

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Section: Resultsmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Arctigenin induces apoptosis in human hepatoblastoma cells

et al. 2019

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“… 213 ). Other agents inducing necroptosis in RIPK3-expressing NB cells are polyphyllin D 214 and d -gal 215 . On the other hand, many NBs have a decreased expression of caspase-8 and low level of proteins involved in necroptosis, especially in the advanced stages, making them also resistant to necroptosis induction 216 .…”

Section: Targeting Nb Via Stimulation Of Various Modes Of Cell Deathmentioning

confidence: 99%

Cell death-based treatment of neuroblastoma

2018

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Neuroblastoma (NB) is the most common solid childhood tumor outside the brain and causes 15% of childhood cancer-related mortality. The main drivers of NB formation are neural crest cell-derived sympathoadrenal cells that undergo abnormal genetic arrangements. Moreover, NB is a complex disease that has high heterogeneity and is therefore difficult to target for successful therapy. Thus, a better understanding of NB development helps to improve treatment and increase the survival rate. One of the major causes of sporadic NB is known to be MYCN amplification and mutations in ALK (anaplastic lymphoma kinase) are responsible for familial NB. Many other genetic abnormalities can be found; however, they are not considered as driver mutations, rather they support tumor aggressiveness. Tumor cell elimination via cell death is widely accepted as a successful technique. Therefore, in this review, we provide a thorough overview of how different modes of cell death and treatment strategies, such as immunotherapy or spontaneous regression, are or can be applied for NB elimination. In addition, several currently used and innovative approaches and their suitability for clinical testing and usage will be discussed. Moreover, significant attention will be given to combined therapies that show more effective results with fewer side effects than drugs targeting only one specific protein or pathway.

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“…The herb Paris polyphylla is a traditional Chinese drug that has heat-clearing and detoxicating effects. Polyphyllin D (PD) is the major component of Paris polyphylla, and it has been used to treat such ailments as convulsions, mastitis, and tumors of the respiratory system, as well as leukemia (3,4,5). Studies have shown that PD functions as an anti-tumor agent through the inhibition of cell proliferation and by inducing apoptosis in several tumor cell types (5,6,7).…”

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SOX7 is involved in polyphyllin D-induced G0/G1 cell cycle arrest through down-regulation of cyclin D1

et al. 2020

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AbstractThe incidence of mortality of prostate cancer (PCa) has been an uptrend in recent years. Our previous study showed that the sex-determining region Y-box 7 (SOX7) was low-expressed and served as a tumor suppressor in PCa cells. Here, we describe the effects of polyphyllin D (PD) on proliferation and cell cycle modifications of PCa cells, and whether SOX7 participates in this process. PC-3 cells were cultured in complete medium containing PD for 12, 24, and 48 h. MTT assay was used to investigate the cytotoxic effects of PD. Cell cycle progression was analyzed using propidium iodide (PI) staining, and protein levels were assayed by Western blot analysis. Our results showed low expression of SOX7 in PCa tissues/cells compared to their non-tumorous counterparts/RWPE-1 cells. Moreover, PD inhibited the proliferation of PC-3 cells in a dose- and time-dependent manner. PD induced G0/G1 cell cycle arrest, while co-treatment with short interfering RNA targeting SOX7 (siSOX7) had reversed this effect. PD downregulated SOX7, cyclin D1, cyclin-dependent kinase 4 (CDK4), and cyclin-dependent kinase 6 (CDK6) expressions in a dose-dependent manner, whereas co-treatment of siSOX7 and PD rescued the PD-inhibited cyclin D1 expression. However, no obvious changes were observed in CDK4 or CDK6 expression. These results indicate that SOX7 is involved in PD-induced PC-3 cell cycle arrest through down-regulation of cyclin D1.

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Polyphyllin D, a steroidal saponin in Paris polyphylla, induces apoptosis and necroptosis cell death of neuroblastoma cells

Cited by 28 publications

References 20 publications

Arctigenin induces apoptosis in human hepatoblastoma cells

Arctigenin induces apoptosis in human hepatoblastoma cells

Cell death-based treatment of neuroblastoma

SOX7 is involved in polyphyllin D-induced G0/G1 cell cycle arrest through down-regulation of cyclin D1

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