Shi-Bing Zhang, M. Hong, Xiao-Yang Sun, Da-xiong Huang, Dan-hua He, Yu-Fei Chen, Yong Yuan, Yongqiang Liu
{"title":"水飞蓟宾通过靶向Skp2对非小细胞肺癌具有治疗作用","authors":"Shi-Bing Zhang, M. Hong, Xiao-Yang Sun, Da-xiong Huang, Dan-hua He, Yu-Fei Chen, Yong Yuan, Yongqiang Liu","doi":"10.15212/amm-2022-0011","DOIUrl":null,"url":null,"abstract":"Silybin (SB), a natural flavonoid isolated from Silybum marianum, has been used to treat hepatic fibrosis in clinical settings and as a dietary supplement, because of its hepatoprotective potential. Numerous studies have shown that SB also exerts promising anticancer effects; however, the anticancer targets of SB and the underlying mechanism were unclear. Herein, we found that SB significantly inhibited the proliferation of non-small cell lung cancer without causing cytotoxicity toward normal Beas-2B bronchial epithelial cells. Mechanistically, SB binds the F-box protein Skp2 and disrupts Skp1-Skp2 interaction, thereby decreasing Skp2 protein levels, inducing accumulation of Skp2 substrates, and leading to G1-phase cell-cycle arrest and the suppression of cell migration. In lung orthotopic xenografts, SB also significantly decreased Skp2 expression and increased p27/Kip1 protein levels. SB administration inhibited tumor growth and metastasis in lung tissue, thus prolonging survival time in mice without causing obvious toxicity. Thus, SB is a potential Skp2-targeting agent that warrants further clinical investigation.","PeriodicalId":72055,"journal":{"name":"Acta materia medica","volume":"1 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2022-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"6","resultStr":"{\"title\":\"Silybin has therapeutic efficacy against non-small cell lung cancer through targeting of Skp2\",\"authors\":\"Shi-Bing Zhang, M. Hong, Xiao-Yang Sun, Da-xiong Huang, Dan-hua He, Yu-Fei Chen, Yong Yuan, Yongqiang Liu\",\"doi\":\"10.15212/amm-2022-0011\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Silybin (SB), a natural flavonoid isolated from Silybum marianum, has been used to treat hepatic fibrosis in clinical settings and as a dietary supplement, because of its hepatoprotective potential. Numerous studies have shown that SB also exerts promising anticancer effects; however, the anticancer targets of SB and the underlying mechanism were unclear. Herein, we found that SB significantly inhibited the proliferation of non-small cell lung cancer without causing cytotoxicity toward normal Beas-2B bronchial epithelial cells. Mechanistically, SB binds the F-box protein Skp2 and disrupts Skp1-Skp2 interaction, thereby decreasing Skp2 protein levels, inducing accumulation of Skp2 substrates, and leading to G1-phase cell-cycle arrest and the suppression of cell migration. In lung orthotopic xenografts, SB also significantly decreased Skp2 expression and increased p27/Kip1 protein levels. SB administration inhibited tumor growth and metastasis in lung tissue, thus prolonging survival time in mice without causing obvious toxicity. Thus, SB is a potential Skp2-targeting agent that warrants further clinical investigation.\",\"PeriodicalId\":72055,\"journal\":{\"name\":\"Acta materia medica\",\"volume\":\"1 1\",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2022-08-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"6\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Acta materia medica\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.15212/amm-2022-0011\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acta materia medica","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.15212/amm-2022-0011","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Silybin has therapeutic efficacy against non-small cell lung cancer through targeting of Skp2
Silybin (SB), a natural flavonoid isolated from Silybum marianum, has been used to treat hepatic fibrosis in clinical settings and as a dietary supplement, because of its hepatoprotective potential. Numerous studies have shown that SB also exerts promising anticancer effects; however, the anticancer targets of SB and the underlying mechanism were unclear. Herein, we found that SB significantly inhibited the proliferation of non-small cell lung cancer without causing cytotoxicity toward normal Beas-2B bronchial epithelial cells. Mechanistically, SB binds the F-box protein Skp2 and disrupts Skp1-Skp2 interaction, thereby decreasing Skp2 protein levels, inducing accumulation of Skp2 substrates, and leading to G1-phase cell-cycle arrest and the suppression of cell migration. In lung orthotopic xenografts, SB also significantly decreased Skp2 expression and increased p27/Kip1 protein levels. SB administration inhibited tumor growth and metastasis in lung tissue, thus prolonging survival time in mice without causing obvious toxicity. Thus, SB is a potential Skp2-targeting agent that warrants further clinical investigation.