Polyphyllin VI, a saponin from Trillium tschonoskii Maxim. induces apoptotic and autophagic cell death via the ROS triggered mTOR signaling pathway in non-small cell lung cancer

Teng, Jin-Feng; Qin, Da-Lian; Mei, Qibing; Qiu, Wen-Qiao; Pan, Rong; Xiong, Rui; Zhao, Yanhong; Law, Betty Yuen‐Kwan; Wong, Vincent Kam Wai; Tang, Yong; Yu, Chong-Lin; Zhang, Feng; Wu, Jianming; Wu, Anguo

doi:10.1016/j.phrs.2019.104396

Cited by 65 publications

(41 citation statements)

References 75 publications

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“…In this study, the anti-proliferative effect of PPVI at 24, 48 and 72 h timepoints was firstly investigated and confirmed in A549 and H1299 cells, which was consistent with our previously reported result ( Figure S1A,B) [29]. Furthermore, the MTT result indicated that PPVI exhibited a similar inhibitive effect among the wild type (WT) EGFR NSCLC cell lines (A549 and H1299) and mutated-EGFR cell line (PC-9) ( Figure S1C).…”

Section: Ppvi Induces Distinct Patterns Of Apoptosis and Lytic Cell Dsupporting

confidence: 92%

“…The PPVI shown in Figure 1A, a main saponin in TTM, has been previously demonstrated by us to significantly inhibit the proliferation of NSCLC via the ROS-triggered, mTOR-mediated apoptotic and autophagic cell death in vitro and in vivo [29]. Recently, emerging evidences indicate that pyroptosis also plays an important role in cancer [30].…”

Section: Ppvi Activates Nlrp3 Inflammasome In A549-bearing Athymic Numentioning

confidence: 83%

“…Therefore, the different effects of PPVI on the activation of the apoptosis pathway may due to the difference of the expression of p53 in A549 and H1299 cells [54]. In addition, we have recently reported that PPVI could significantly suppress the proliferation of NSCLC via the induction of apoptosis and autophagy in vitro and in vivo, which was regulated by the increased ROS levels and its resultant downregulation of the mTOR-signaling pathway [29]. Further study in the current animal experiment found that the NLRP3 inflammasome was activated in PPVI-administrated, A549-bearing athymic nude mice.…”

Section: Discussionmentioning

confidence: 99%

“…In this study, all the animal experiments were approved with a No. 201903-143 by the Animal Ethics Committee (AEC) of the Southwest Medical University, and performed as described previously [29]. Briefly, six week old female and male athymic nude mice purchased from Chengdu Dashuo Experimental Animal Co., Ltd. (Chengdou, China) were maintained in pathogen-free conditions.…”

Section: Animal and Drug Administrationmentioning

confidence: 99%

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Polyphyllin VI Induces Caspase-1-Mediated Pyroptosis via the Induction of ROS/NF-κB/NLRP3/GSDMD Signal Axis in Non-Small Cell Lung Cancer

Teng

Mei

Zhou

et al. 2020

Cancers

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206

127

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Trillium tschonoskii Maxim (TTM), a traditional Chinese medicine, has been demonstrated to have a potent anti-tumor effect. Recently, polyphyllin VI (PPVI), a main saponin isolated from TTM, was reported by us to significantly suppress the proliferation of non-small cell lung cancer (NSCLC) via the induction of apoptosis and autophagy in vitro and in vivo. In this study, we further found that the NLRP3 inflammasome was activated in PPVI administrated A549-bearing athymic nude mice. As is known to us, pyroptosis is an inflammatory form of caspase-1-dependent programmed cell death that plays an important role in cancer. By using A549 and H1299 cells, the in vitro effect and action mechanism by which PPVI induces activation of the NLRP3 inflammasome in NSCLC were investigated. The anti-proliferative effect of PPVI in A549 and H1299 cells was firstly measured and validated by MTT assay. The activation of the NLRP3 inflammasome was detected by using Hoechst33324/PI staining, flow cytometry analysis and real-time live cell imaging methods. We found that PPVI significantly increased the percentage of cells with PI signal in A549 and H1299, and the dynamic change in cell morphology and the process of cell death of A549 cells indicated that PPVI induced an apoptosis-to-pyroptosis switch, and, ultimately, lytic cell death. In addition, belnacasan (VX-765), an inhibitor of caspase-1, could remarkably decrease the pyroptotic cell death of PPVI-treated A549 and H1299 cells. Moreover, by detecting the expression of NLRP3, ASC, caspase-1, IL-1β, IL-18 and GSDMD in A549 and h1299 cells using Western blotting, immunofluorescence imaging and flow cytometric analysis, measuring the caspase-1 activity using colorimetric assay, and quantifying the cytokines level of IL-1β and IL-18 using ELISA, the NLRP3 inflammasome was found to be activated in a dose manner, while VX-765 and necrosulfonamide (NSA), an inhibitor of GSDMD, could inhibit PPVI-induced activation of the NLRP3 inflammasome. Furthermore, the mechanism study found that PPVI could activate the NF-κB signaling pathway via increasing reactive oxygen Cancers 2020, 12, 193 2 of 27 species (ROS) levels in A549 and H1299 cells, and N-acetyl-L-cysteine (NAC), a scavenger of ROS, remarkably inhibited the cell death, and the activation of NF-κB and the NLRP3 inflammasome in PPVI-treated A549 and H1299 cells. Taken together, these data suggested that PPVI-induced, caspase-1-mediated pyroptosis via the induction of the ROS/NF-κB/NLRP3/GSDMD signal axis in NSCLC, which further clarified the mechanism of PPVI in the inhibition of NSCLC, and thereby provided a possibility for PPVI to serve as a novel therapeutic agent for NSCLC in the future.

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Section: Ppvi Induces Distinct Patterns Of Apoptosis and Lytic Cell Dsupporting

confidence: 92%

Section: Ppvi Activates Nlrp3 Inflammasome In A549-bearing Athymic Numentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Animal and Drug Administrationmentioning

confidence: 99%

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Polyphyllin VI Induces Caspase-1-Mediated Pyroptosis via the Induction of ROS/NF-κB/NLRP3/GSDMD Signal Axis in Non-Small Cell Lung Cancer

Teng

Mei

Zhou

et al. 2020

Cancers

Self Cite

206

127

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“…Polyphyllin VI (PPVI) ( Figure 1A, a steroidal saponin isolated from Paris polyphylla), has been shown to have anti-cancer against various types of malignancies. For example, Teng et al 6 demonstrated that PPVI could suppress the proliferation of non-small-cell lung cancer, while in hepatocellular carcinoma, it was found to induce apoptosis via the Fas death pathway. 7 However, the effect of PPVI on glioma remains unknown.…”

Section: Introductionmentioning

confidence: 99%

<p>Polyphyllin VI Induces Apoptosis and Autophagy via Reactive Oxygen Species Mediated JNK and P38 Activation in Glioma</p>

Liu

Chai

et al. 2020

OTT

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Background: Polyphyllin VI (PPVI), a bioactive component derived from a traditional Chinese herb Paris polyphylla, exhibits potential antitumor activity against hepatocellular carcinoma, as well as breast and lung cancers. However, its effect on glioma remains unknown. Methods: Five glioma cell lines (U251, U343, LN229, U87 and HEB) and an animal model were employed in the study. Anti-proliferation effects of PPVI were first determined using CCK-8 cell proliferation and clone formation assays, then reactive oxygen species (ROS), cell cycle progression and apoptosis effects measured by flow cytometry. The effect of PPVI on protein expression was quantified by Western blot analysis. Results: Data showed that PPVI inhibited the proliferation of glioma cell lines by modulating the G2/M phase. Additionally, incubation of cells with PPVI promoted apoptosis, autophagy, increased accumulation of ROS and activated ROS-modulated JNK and p38 pathways. On the other hand, N-acetyl cysteine, a ROS inhibitor, attenuated PPVItriggered effects. Furthermore, JNK and p38 inhibitors ameliorated PPVI-triggered autophagy and apoptosis in glioma cells. In vivo assays showed that PPVI inhibited tumor growth of U87 cell line in nude mice. Conclusion: Overall, these data suggested that PPVI might be an effective therapeutic agent for glioma.

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Multimodal integrated strategy for the discovery and identification of antiplatelet aggregation Q‐markers in Paris polyphylla var. yunnanensis

Li,

Wen,

Yang

et al. 2024

Biomedical Chromatography

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To enhance the quality evaluation and control of traditional Chinese medicine (TCM) and ensure the safety and efficacy of clinical medication, it is imperative to establish a comprehensive quality assessment method aligned with TCM efficacy. This study uses a representative Chinese medicine with multi‐origin and multi‐efficacy, Paris polyphylla var. yunnanensis (PY), as an illustrative example. Surprisingly, despite the high fingerprint similarity among the 12 batches of PY samples collected from various regions in Yunnan, a notable variation in the composition and content of components was observed. The chromatographic analysis identified seven common peaks, namely, polyphyllin I, polyphyllin II, polyphyllin V, polyphyllin VI, polyphyllin VII, polyphyllin H, and polyphyllin D. In the bioactivity evaluation, an in vitro antiplatelet aggregation model induced by adenosine diphosphate was established, showcasing excellent stability. The maximum antiplatelet aggregation inhibition rate for all PY samples consistently remained stable at 73.1%–99.1%. However, the 50% inhibitory concentration (IC50) values exhibited a range from 1.615 to 18.200 mg/mL. This approach not only meets high‐throughput screening requirements but also demonstrates remarkable discrimination. The results of chemical and bioactivity evaluations were analyzed using hierarchical cluster analysis and canonical correlation analysis. Polyphyllin I, polyphyllin II, polyphyllin VII, polyphyllin H, and polyphyllin D were identified as the Q‐markers for antiplatelet aggregation in PY samples. Validation of the bioactivity for these monomer components aligned with the previously mentioned findings. Notably, this study established a spectrum–effect model for PY samples, enhancing the scientific robustness of the quality evaluation method. Furthermore, these findings offer valuable research insights for improving the quality assessment of other TCMs.

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Polyphyllin VI, a saponin from Trillium tschonoskii Maxim. induces apoptotic and autophagic cell death via the ROS triggered mTOR signaling pathway in non-small cell lung cancer

Cited by 65 publications

References 75 publications

Polyphyllin VI Induces Caspase-1-Mediated Pyroptosis via the Induction of ROS/NF-κB/NLRP3/GSDMD Signal Axis in Non-Small Cell Lung Cancer

Polyphyllin VI Induces Caspase-1-Mediated Pyroptosis via the Induction of ROS/NF-κB/NLRP3/GSDMD Signal Axis in Non-Small Cell Lung Cancer

<p>Polyphyllin VI Induces Apoptosis and Autophagy via Reactive Oxygen Species Mediated JNK and P38 Activation in Glioma</p>

Multimodal integrated strategy for the discovery and identification of antiplatelet aggregation Q‐markers in Paris polyphylla var. yunnanensis

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