Polyphyllin I, a lethal partner of Palbociclib, suppresses non-small cell lung cancer through activation of p21/CDK2/Rb pathway <i>in vitro</i> and <i>in vivo</i>

Shen, Zhengchao; Wang, Jian; Ke, Kunbin; Chen, Rong; Zuo, Ai‐Xue; Zhang, Rongping; Wan, Weiping; Xie, Xinhua; Li, Xuhua; Song, Na; Fu, Hao; Zhang, Zhiwei; Cai, EnLi; Shen, Jihong; Shi, Xi‐Nan

doi:10.1080/15384101.2021.1991121

Cited by 14 publications

(8 citation statements)

References 31 publications

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“…In recent years, researchers have investigated the active ingredients and pharmacological mechanisms of PPI. PPI has many pharmacological effects, such as antitumor [ 15 , 16 ], anti-inflammatory [ 17 ], antibacterial [ 18 , 19 ], anti-Alzheimer's disease, and immune regulation [ 13 ]. PPI is also effective against C. albicans , but the antifungal mechanism remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Polyphyllin I Effects Candida albicans via Inhibition of Virulence Factors

Sun

Wang

et al. 2023

Evidence-Based Complementary and Alternative Medicine

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Paris polyphylla is often used in Chinese medicine to treat conditions such as carbuncles, trauma, snake bites, and mosquito bites. In the present study, we investigated the effect and mechanism of the morphological transition and extracellular phospholipase activity of Candida albicans treated with polyphyllin I (PPI). First, the minimum inhibitory concentration and antifungal activity of PPI were evaluated using the multiple microdilution method and time-killing assays. Then, the effect of PPI on the morphological transition of Candida albicans in Spider liquid medium and Sabouraud-dextrose liquid medium containing 10% fetal bovine serum was observed under an inverted microscope and by scanning electron microscopy. Finally, egg yolk agar plates were used to evaluate extracellular phospholipase activity. Gene expression was detected by real-time quantitative polymerase chain reaction analysis. Our results suggest that PPI inhibited the transition from the yeast to the hyphal stage and decreased secreted aspartyl proteinase activity. We further confirmed that PPI significantly downregulated the expression of extracellular phospholipase genes and cAMP-PKA signaling pathway-related genes. Taken together, our results suggest that PPI exerts anti-Candida albicans activity by inhibiting virulence characteristics, including the yeast-to-hyphal transition and the secretion of aspartyl proteases and phospholipases. The study results also indicated that PPI could be a promising therapeutic strategy for Candida albicans.

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Section: Introductionmentioning

confidence: 99%

Polyphyllin I Effects Candida albicans via Inhibition of Virulence Factors

Sun

Wang

et al. 2023

Evidence-Based Complementary and Alternative Medicine

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“…Polyphyllin series, including PPI, can be derived from Rhizoma paridis and are also anti-tumorous ( Li et al, 2023 ). Mechanistically, PPI activated the AMPK or p21/CDK2/Rb pathway to inhibit the growth of non-small cell lung cancer ( Wu et al, 2020 ; Shen et al, 2021 ), suppressed the tumoral angiogenesis through the Twist1/VE-cadherin pathway, and induced apoptosis in hepatocellular carcinoma ( Shi et al, 2015 ; Xiao et al, 2018 ; Zeng et al, 2020 ). Furthermore, it induced autophagy and apoptosis in the gastric cancer and colon cancer cells by inhibiting the PDK1/Akt/mTOR signaling ( He et al, 2019 ; Luo et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

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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“…Drug targets of the active ingredients in Chonglou (dioscin ( Tao et al, 2018 ; Ding et al, 2020 ; Wu et al, 2020 ), gracillin ( Liu et al, 2021 ; Yang J. et al, 2021 ; Yang L. et al, 2021 ), polyphyllin I ( Chang et al, 2017 ; Tian et al, 2020 ; Lai et al, 2021 ; Shen et al, 2021 ), polyphyllin II ( Niu et al, 2020 ), polyphyllin III ( Zhou et al, 2021 ), polyphyllin VI ( Liu et al, 2020 ; Teng et al, 2020 ), polyphyllin VII ( He et al, 2020 ; Zhao et al, 2021 ) and polyphyllin H) were collected by using the online tools ( Su et al, 2019 ), including PubChem ( https://pubchem.ncbi.nlm.nih.gov/ ), Swiss Target Prediction ( http://www.swisstargetprediction.ch/index.php ) and TargetNet ( http://targetnet.scbdd.com/home/index/ ).…”

Section: Methodsmentioning

confidence: 99%

“…The expression differences of m 6 A-related genes, including ALKBH5, HNRNPC, METTL14, METTL3, YTHDF2, IGF2BP1, IGF2BP3, METTL16, RBMX, IGF2BP2, and HNRNPA2BA, were analyzed between the low-risk and the high-risk groups mentioned above in LUAD patients (Huang et al, 2020). (Tao et al, 2018;Ding et al, 2020;Wu et al, 2020), gracillin (Liu et al, 2021;Yang J. et al, 2021;, polyphyllin I (Chang et al, 2017;Tian et al, 2020;Lai et al, 2021;Shen et al, 2021), polyphyllin II (Niu et al, 2020), polyphyllin III (Zhou et al, 2021), polyphyllin VI (Liu et al, 2020;Teng et al, 2020), polyphyllin VII (He et al, 2020;Zhao et al, 2021) and polyphyllin H) were collected by using the online tools (Su et al, 2019), including PubChem (https://pubchem. The overlapping gene set between the drug targets of Chonglou active ingredients with the EMT-LUAD related genes were enquired in the STRING database (version 11.5) (EMT-LUAD- Frontiers in Genetics frontiersin.org Chonglou related genes), which was used for the following proteinprotein interactions (PPI) network, hub genes and enrichment analyses.…”

Section: Correlation Analysis Between N6methyladenosine (M6a)-related...mentioning

confidence: 99%

Identification and vitro verification of the potential drug targets of active ingredients of Chonglou in the treatment of lung adenocarcinoma based on EMT-related genes

Zhao

Zhao²,

Chang³

et al. 2023

Front. Genet.

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Lung adenocarcinoma (LUAD) is the main histological type of lung cancer with an unfavorable survival rate. Metastasis is the leading LUAD-related death with Epithelial-Mesenchymal Transition (EMT) playing an essential role. The anticancer efficacies of the active ingredients in Chonglou have been widely reported in various cancers. However, the potential therapeutic targets of the Chonglou active ingredients in LUAD patients remain unknown. Here, the network pharmacology and bioinformatics were performed to analyze the associations of the clinical characteristics, immune infiltration factors and m6A-related genes with the EMT-related genes associated with LUAD (EMT-LUAD related genes), and the molecular docking, STRING, GO, and KEGG enrichment for the drug targets of Chonglou active ingredients associated with EMT (EMT-LUAD-Chonglou related genes). And, cell viability analysis and cell invasion and infiltration analysis were used to confirm the theoretical basis of this study. A total of 166 EMT-LUAD related genes were identified and a multivariate Cox proportional hazards regression model with a favorable predictive accuracy was constructed. Meanwhile, the immune cell infiltration, immune cell subsets, checkpoint inhibitors and the expression of m6A-related genes were significantly associated with the risk scores for EMT-LUAD related genes with independent significant prognostic value of all included LUAD patients. Furthermore, 12 EMT-LUAD-Chonglou related genes with five core drug targets were identified, which participated in LUAD development through extracellular matrix disassembly, collagen metabolic process, collagen catabolic process, extracellular matrix organization, extracellular structure organization and inflammatory response. Moreover, we found that the active ingredients of Chonglou could indeed inhibit the progression of lung adenocarcinoma cells. These results are oriented towards EMT-related genes to achieve a better understanding of the role of Chonglou and its targets in osteosarcoma development and metastasis, thus guiding future preclinical studies and facilitating clinical translation of LUAD treatment.

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Polyphyllin I, a lethal partner of Palbociclib, suppresses non-small cell lung cancer through activation of p21/CDK2/Rb pathway in vitro and in vivo

Cited by 14 publications

References 31 publications

Polyphyllin I Effects Candida albicans via Inhibition of Virulence Factors

Polyphyllin I Effects Candida albicans via Inhibition of Virulence Factors

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

Identification and vitro verification of the potential drug targets of active ingredients of Chonglou in the treatment of lung adenocarcinoma based on EMT-related genes

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