Polyphyllin I suppresses proliferation and promotes apoptosis of gastric cancer cell by inhibiting stat3 phosphorylation

Han, Jikhyon; Kan, Jie; Wang, Xinguo; Yuan, Qingling; Song, Xian‐Rong; Huang, Min; Wu, Hao

doi:10.21037/tcr-20-66

Cited by 14 publications

(13 citation statements)

References 24 publications

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“…Previous reports showed that PPI inhibited the tumor growth via several mechanisms ( Dong et al, 2018 ; Zhang et al, 2018 ; Han et al, 2020 ). In this study, we first confirmed that PPI indeed suppressed both AGS and MKN-45 cancer cell growth in vitro in a dose-dependent manner based on MTT assays ( Figure 2A, B ).…”

Section: Resultsmentioning

confidence: 99%

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Polyphyllin I suppresses the gastric cancer growth by promoting cancer cell ferroptosis

et al. 2023

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Background: Ferroptosis is a new form of regulated cell death characterized by the accumulation of iron-dependent lipid peroxides and membrane damages. Recent studies have identified an important role for cancer cell ferroptosis in antitumor therapy. On the other hand, polyphyllin I (PPI) has been reported to exert antitumor effects on some types of cancers. However, it remains unknown whether or not PPI regulates cancer cell ferroptosis.Methods: Two types of human gastric cancer cells (AGS and MKN-45) were used to establish tumor xenograft models in nude mice that were treated with polyphyllin I (PPI) to observe tumor growth, while cells also were cultured for in vitro studies. Ferroptosis, based on the intracellular ROS/lipid ROS production and accumulation of ferrous ions, was detected using a fluorescence microscope and flow cytometer, while the expression of NRF2/FTH1 was measured using Western blotting assays.Results: Here we found that PPI inhibited the gastric cancer growth in vivo and in vitro while increasing the intracellular reactive oxygen species (ROS)/lipid peroxides and ferrous ions in the gastric cancer cells. PPI also decreased the levels of nuclear factor erythroid 2-related factor 2 (NRF2) and ferritin heavy chain 1 (FTH1) in gastric cancer cells in vitro. Moreover, liproxstain-1, an inhibitor of cell ferroptosis, mostly reversed the cell ferroptosis and tumor growth arrest induced by PPI. Finally, the effects of PPI on cancer cell ferroptosis were diminished by the overexpression of NRF2.Conclusion: For the first time, our results have demonstrated that PPI exerts its antitumor activity on the gastric cancer by, at least partially, inducing cancer cell ferroptosis via regulating NRF2/FTH1 pathway. These findings may be implicated for clinical replacement therapy of the gastric cancer.

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Section: Resultsmentioning

confidence: 99%

“…The transcriptional and signal pathways initiated by PPI may include STAT3, AMPK, FOXO3 and PI3K/Akt, etc. ( Han et al, 2015 ; Li et al, 2016 ; Lou et al, 2017 ; Liu et al, 2018 ; Han et al, 2020 ; Li et al, 2020 ; Lai et al, 2021 ). However, there has been no any report on a potential impact of PPI on cancer cell ferroptosis.…”

Section: Introductionmentioning

confidence: 99%

Polyphyllin I suppresses the gastric cancer growth by promoting cancer cell ferroptosis

et al. 2023

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“…STAT3 has been proposed as a pathogenic factor and therapeutic target of CRC [ 20 ]. PPI, another important active component extracted from Rhizoma Paridis , has been shown to inhibit STAT3 activation in gastric cancer cells [ 12 ]. In this study, we found that PPII also suppressed the phosphorylation/activation of STAT3 in human CRC cells and the HCT116 xenografts.…”

Section: Discussionmentioning

confidence: 99%

“…Steroid saponins, such as polyphyllin I (PPI), II (PPII), VI (PPVI), and VII (PPVII), are active ingredients identified in Rhizoma Paridis . Among these polyphyllins, PPI has a significant therapeutic effect on hepatocellular carcinoma, CRC, melanoma, prostate cancer, and gastric cancer by inducing cell cycle arrest, apoptosis, and autophagy, as well as by inhibiting the activation of STAT3 and the PI3K/AKT/mTOR signaling pathways [ 11 , 12 , 13 , 14 ]. PPVI has been demonstrated to provoke apoptosis and autophagy in human osteosarcoma cells [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Polyphyllin II Induces Protective Autophagy and Apoptosis via Inhibiting PI3K/AKT/mTOR and STAT3 Signaling in Colorectal Cancer Cells

Sun

Jiang

et al. 2022

IJMS

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Polyphyllin II (PPII) is a natural steroidal saponin occurring in Rhizoma Paridis. It has been demonstrated to exhibit anti-cancer activity against a variety of cancer cells. However, the anti-colorectal cancer (CRC) effects and mechanism of action of PPII are rarely reported. In the present study, we showed that PPII inhibited the proliferation of HCT116 and SW620 cells. Moreover, PPII induced G2/M-phase cell cycle arrest and apoptosis, as well as protective autophagy, in CRC cells. We found that PPII-induced autophagy was associated with the inhibition of PI3K/AKT/mTOR signaling. Western blotting results further revealed that PPII lowered the protein levels of phospho-Src (Tyr416), phospho-JAK2 (Tyr1007/1008), phospho-STAT3 (Tyr705), and STAT3-targeted molecules in CRC cells. The overactivation of STAT3 attenuated the cytotoxicity of PPII against HCT116 cells, indicating the involvement of STAT3 inhibition in the anti-CRC effects of PPII. PPII (0.5 mg/kg or 1 mg/kg, i.p. once every 3 days) suppressed HCT116 tumor growth in nude mice. In alignment with the in vitro results, PPII inhibited proliferation, induced apoptosis, and lowered the protein levels of phospho-STAT3, phospho-AKT, and phospho-mTOR in xenografts. These data suggest that PPII could be a potent therapeutic agent for the treatment of CRC.

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“…For example, application of inhibitors targeting the Janus kinase 2/signal transducer and activator of transcription 3 (JAK/STAT3) pathway (e.g., AG490) may have a strong effect in anti-gastric cancer therapy (Bogani et al, 2013). Studies have confirmed that polyphyllin I mainly inhibits the phosphorylation of STAT3 in a way that inhibits the expression of apoptosis-related protein, such as BCL2, and induces apoptosis of gastric cancer cells (Han et al, 2020). Another experimental study confirmed that polyphyllin I promotes the transformation of mesenchymal cells to epithelial cells, thereby partially inhibiting the migration and invasion of gastric cancer cells.…”

Section: Other Antitumor Activities Of Polyphyllin Imentioning

confidence: 99%

Therapeutic effects on cancer of the active ingredients in rhizoma paridis

Jia

Zhu

et al. 2023

Front. Pharmacol.

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Cancer is a major threat to human health, with high mortality and a low cure rate, continuously challenging public health worldwide. Extensive clinical application of traditional Chinese medicine (TCM) for patients with poor outcomes of radiotherapy and chemotherapy provides a new direction in anticancer therapy. Anticancer mechanisms of the active ingredients in TCM have also been extensively studied in the medical field. As a type of TCM against cancer, Rhizoma Paridis (Chinese name: Chonglou) has important antitumor effects in clinical application. The main active ingredients of Rhizoma Paridis (e.g., total saponins, polyphyllin I, polyphyllin II, polyphyllin VI, and polyphyllin VII) have shown strong antitumor activities in various cancers, such as breast cancer, lung cancer, colorectal cancer, hepatocellular carcinoma (HCC), and gastric cancer. Rhizoma Paridis also has low concentrations of certain other active ingredients with antitumor effects, such as saponins polyphyllin E, polyphyllin H, Paris polyphylla-22, gracillin, and formosanin-C. Many researchers have studied the anticancer mechanism of Rhizoma Paridis and its active ingredients. This review article describes research progress regarding the molecular mechanism and antitumor effects of the active ingredients in Rhizoma Paridis, suggesting that various active ingredients in Rhizoma Paridis may be potentially therapeutic against cancer.

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Polyphyllin I suppresses proliferation and promotes apoptosis of gastric cancer cell by inhibiting stat3 phosphorylation

Cited by 14 publications

References 24 publications

Polyphyllin I suppresses the gastric cancer growth by promoting cancer cell ferroptosis

Polyphyllin I suppresses the gastric cancer growth by promoting cancer cell ferroptosis

Polyphyllin II Induces Protective Autophagy and Apoptosis via Inhibiting PI3K/AKT/mTOR and STAT3 Signaling in Colorectal Cancer Cells

Therapeutic effects on cancer of the active ingredients in rhizoma paridis

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