Paris saponin VII extracted from Trillium tschonoskii induces autophagy and apoptosis in NSCLC cells
Trillium tschonoskii Maxim, a perennial herb of the Trilliaceae, has been widely used to treat inflammation, hypertension and cancer. We investigated Paris saponin VII's (PS VII), isolated from Trillium tschonoskii Maxim, function in mediating autophagy and apoptosis in NSCLC cells. We treated...
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Published in | Journal of ethnopharmacology Vol. 248; p. 112304 |
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Abstract | Trillium tschonoskii Maxim, a perennial herb of the Trilliaceae, has been widely used to treat inflammation, hypertension and cancer. We investigated Paris saponin VII's (PS VII), isolated from Trillium tschonoskii Maxim, function in mediating autophagy and apoptosis in NSCLC cells.
We treated various NSCLC cells with different concentrations of PS Ⅶ and then measure the cell apoptosis by using flow cytometry assays and western blot. Autophagy were investigated by using western blot, transmission electron microscopy and immunofluorescence analysis. We also use a xenograft model of nude mice to measure the effect of PS Ⅶ in vivo.
Treatment with PS Ⅶ significantly inhibit NSCLC cell growth, especially for A549 (IC50 = 1.53 μM). Moreover, PS VII induces caspase-dependent apoptosis and autophagy through AMPK-ULK1 pathway. After blocking autophagy by 3-methyladenine (3-MA), PS VII induced cell death was significantly increased. In vivo, the co-treatment with PS VII and 3-MA dramatically inhibited A549 tumor growth in immune deficient mice and has similar inhibition rates as cisplatin group.
Our results suggest that a combination of PS VII and autophagy inhibitor may be a potential anticancer strategy in the NSCLC therapy.
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AbstractList | Trillium tschonoskii Maxim, a perennial herb of the Trilliaceae, has been widely used to treat inflammation, hypertension and cancer. We investigated Paris saponin VII's (PS VII), isolated from Trillium tschonoskii Maxim, function in mediating autophagy and apoptosis in NSCLC cells.
We treated various NSCLC cells with different concentrations of PS Ⅶ and then measure the cell apoptosis by using flow cytometry assays and western blot. Autophagy were investigated by using western blot, transmission electron microscopy and immunofluorescence analysis. We also use a xenograft model of nude mice to measure the effect of PS Ⅶ in vivo.
Treatment with PS Ⅶ significantly inhibit NSCLC cell growth, especially for A549 (IC
= 1.53 μM). Moreover, PS VII induces caspase-dependent apoptosis and autophagy through AMPK-ULK1 pathway. After blocking autophagy by 3-methyladenine (3-MA), PS VII induced cell death was significantly increased. In vivo, the co-treatment with PS VII and 3-MA dramatically inhibited A549 tumor growth in immune deficient mice and has similar inhibition rates as cisplatin group.
Our results suggest that a combination of PS VII and autophagy inhibitor may be a potential anticancer strategy in the NSCLC therapy. ETHNOPHARMACOLOGICAL RELEVANCETrillium tschonoskii Maxim, a perennial herb of the Trilliaceae, has been widely used to treat inflammation, hypertension and cancer. We investigated Paris saponin VII's (PS VII), isolated from Trillium tschonoskii Maxim, function in mediating autophagy and apoptosis in NSCLC cells. MATERIALS AND METHODSWe treated various NSCLC cells with different concentrations of PS Ⅶ and then measure the cell apoptosis by using flow cytometry assays and western blot. Autophagy were investigated by using western blot, transmission electron microscopy and immunofluorescence analysis. We also use a xenograft model of nude mice to measure the effect of PS Ⅶ in vivo. RESULTSTreatment with PS Ⅶ significantly inhibit NSCLC cell growth, especially for A549 (IC50 = 1.53 μM). Moreover, PS VII induces caspase-dependent apoptosis and autophagy through AMPK-ULK1 pathway. After blocking autophagy by 3-methyladenine (3-MA), PS VII induced cell death was significantly increased. In vivo, the co-treatment with PS VII and 3-MA dramatically inhibited A549 tumor growth in immune deficient mice and has similar inhibition rates as cisplatin group. CONCLUSIONOur results suggest that a combination of PS VII and autophagy inhibitor may be a potential anticancer strategy in the NSCLC therapy. Trillium tschonoskii Maxim, a perennial herb of the Trilliaceae, has been widely used to treat inflammation, hypertension and cancer. We investigated Paris saponin VII's (PS VII), isolated from Trillium tschonoskii Maxim, function in mediating autophagy and apoptosis in NSCLC cells. We treated various NSCLC cells with different concentrations of PS Ⅶ and then measure the cell apoptosis by using flow cytometry assays and western blot. Autophagy were investigated by using western blot, transmission electron microscopy and immunofluorescence analysis. We also use a xenograft model of nude mice to measure the effect of PS Ⅶ in vivo. Treatment with PS Ⅶ significantly inhibit NSCLC cell growth, especially for A549 (IC50 = 1.53 μM). Moreover, PS VII induces caspase-dependent apoptosis and autophagy through AMPK-ULK1 pathway. After blocking autophagy by 3-methyladenine (3-MA), PS VII induced cell death was significantly increased. In vivo, the co-treatment with PS VII and 3-MA dramatically inhibited A549 tumor growth in immune deficient mice and has similar inhibition rates as cisplatin group. Our results suggest that a combination of PS VII and autophagy inhibitor may be a potential anticancer strategy in the NSCLC therapy. [Display omitted] |
ArticleNumber | 112304 |
Author | Wu, Juan Zhu, Deqiu Tong, Shanshan Qian, Shijing Qi, Zhan Zhang, Yan Tian, Lulu Chen, Beilei |
Author_xml | – sequence: 1 givenname: Shijing surname: Qian fullname: Qian, Shijing email: qiansjing@163.com organization: Department of Pharmacy, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, PR China – sequence: 2 givenname: Shanshan surname: Tong fullname: Tong, Shanshan email: 724615936@qq.com organization: Department of Pharmacy, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, PR China – sequence: 3 givenname: Juan surname: Wu fullname: Wu, Juan email: tjyjk203@163.com organization: Department of Pharmacy, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, PR China – sequence: 4 givenname: Lulu surname: Tian fullname: Tian, Lulu email: lulongtim@126.com organization: Department of Pharmacy, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, PR China – sequence: 5 givenname: Zhan surname: Qi fullname: Qi, Zhan email: qizhn19821212@126.com organization: Department of Pharmacy, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, PR China – sequence: 6 givenname: Beilei surname: Chen fullname: Chen, Beilei email: you27622376@126.com organization: Department of Pharmacy, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, PR China – sequence: 7 givenname: Deqiu surname: Zhu fullname: Zhu, Deqiu email: zdq_0726@163.com organization: Department of oncology, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, PR China – sequence: 8 givenname: Yan surname: Zhang fullname: Zhang, Yan email: yanzhang20190617@163.com organization: Department of oncology, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, PR China |
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Cites_doi | 10.3322/caac.21492 10.1371/journal.pone.0083611 10.1016/S0025-6196(11)60735-0 10.1371/journal.pone.0030312 10.1200/JCO.2007.14.0988 10.1126/science.1196371 10.1016/j.phymed.2013.04.014 10.1038/nrc2088 10.1002/ptr.5389 10.1016/j.jep.2018.12.018 10.1016/j.cell.2014.11.006 10.1038/nrendo.2014.35 10.3892/ijo_00000648 10.1056/NEJMra1703413 10.1016/j.jep.2014.04.049 10.3390/cancers3022630 10.1016/j.bcp.2014.01.018 10.1038/446745a 10.1016/j.cellsig.2014.08.019 10.1158/0008-5472.CAN-09-1751 |
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Pharmacol. doi: 10.1016/j.bcp.2014.01.018 contributor: fullname: Li – volume: 446 start-page: 745 year: 2007 ident: 10.1016/j.jep.2019.112304_bib10 article-title: Cell biology: autophagy and cancer publication-title: Nature doi: 10.1038/446745a contributor: fullname: Levine – volume: 26 start-page: 2694 year: 2014 ident: 10.1016/j.jep.2019.112304_bib7 article-title: The role of pi3k/akt/mtor pathway in the modulation of autophagy and the clearance of protein aggregates in neurodegeneration publication-title: Cell. Signal. doi: 10.1016/j.cellsig.2014.08.019 contributor: fullname: Heras-Sandoval – volume: 70 start-page: 288 year: 2010 ident: 10.1016/j.jep.2019.112304_bib2 article-title: Azd8055 is a potent, selective, and orally bioavailable atp-competitive mammalian target of rapamycin kinase inhibitor with in vitro and in vivo antitumor activity publication-title: Cancer Res. doi: 10.1158/0008-5472.CAN-09-1751 contributor: fullname: Chresta |
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Snippet | Trillium tschonoskii Maxim, a perennial herb of the Trilliaceae, has been widely used to treat inflammation, hypertension and cancer. We investigated Paris... ETHNOPHARMACOLOGICAL RELEVANCETrillium tschonoskii Maxim, a perennial herb of the Trilliaceae, has been widely used to treat inflammation, hypertension and... |
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SubjectTerms | AMPK Animals Antineoplastic Agents, Phytogenic - pharmacology Antineoplastic Agents, Phytogenic - therapeutic use Apoptosis Apoptosis - drug effects Autophagy Autophagy - drug effects Carcinoma, Non-Small-Cell Lung - drug therapy Cell Line, Tumor Humans Lung Neoplasms - drug therapy Mice, Inbred BALB C Mice, Nude NSCLC Saponins - pharmacology Saponins - therapeutic use Trillium |
Title | Paris saponin VII extracted from Trillium tschonoskii induces autophagy and apoptosis in NSCLC cells |
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