Jie Li, Mingyuan Xu, Nanhui Wu, Fei Wu, Jiashe Chen, Xiaoxiang Xu, Fei Tan, Yeqiang Liu
{"title":"柑橘源薯蓣皂苷对黑色素瘤的作用:通过抑制PI3K/Akt/mTOR通路诱导细胞凋亡和自噬。","authors":"Jie Li, Mingyuan Xu, Nanhui Wu, Fei Wu, Jiashe Chen, Xiaoxiang Xu, Fei Tan, Yeqiang Liu","doi":"10.2174/0118715206360266250115065234","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Diosmetin (DIOS) is a naturally abundant flavonoid and possesses various biological activities that hold promise as an anti-cancer agent. However, the anti-cancer activities and underlying mechanism of DIOS on cutaneous melanoma remain unclear.</p><p><strong>Objective: </strong>This study seeks to explore the anti-tumor effect and mechanism of DIOS in cutaneous melanoma.</p><p><strong>Methods: </strong>Here, a variety of in vitro and in vivo experiments, combined with RNA sequencing (RNA-seq), were employed to ascertain the potential anti-cutaneous melanoma capacity and mechanism of DIOS.</p><p><strong>Results: </strong>The results demonstrated that DIOS considerably impeded cell proliferation and triggered cell apoptosis in a dose- and time-dependent manner. Concurrently, DIOS markedly elevated the expression of pro-apoptotic proteins (Cleaved caspase-3, Bax, Cleaved PARP, and Cleaved caspase-9) and downregulated the expression of Bcl-2. Additionally, DIOS markedly upregulated the protein expressions of LC3B-II and Atg5, while downregulating p62 protein expression. Notably, pre-treatment with an autophagy inhibitor significantly inhibited DIOSinduced cell apoptosis and autophagy. Mechanistically, DIOS was identified to repress the PI3K/Akt/mTOR signaling pathway by western blot analyses and RNA-seq. Finally, in vivo experiments using a syngeneic mouse model confirmed the anti-tumor effect of DIOS, which exhibited high levels of apoptosis and autophagy.</p><p><strong>Conclusion: </strong>These findings propose that DIOS acts as a potential melanoma therapy that exerts its anti-tumor effects by triggering apoptosis and autophagy via inhibition of the PI3K/Akt/mTOR pathway.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6000,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Effects of Citrus-derived Diosmetin on Melanoma: Induction of Apoptosis and Autophagy Mediated by PI3K/Akt/mTOR Pathway Inhibition.\",\"authors\":\"Jie Li, Mingyuan Xu, Nanhui Wu, Fei Wu, Jiashe Chen, Xiaoxiang Xu, Fei Tan, Yeqiang Liu\",\"doi\":\"10.2174/0118715206360266250115065234\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Diosmetin (DIOS) is a naturally abundant flavonoid and possesses various biological activities that hold promise as an anti-cancer agent. However, the anti-cancer activities and underlying mechanism of DIOS on cutaneous melanoma remain unclear.</p><p><strong>Objective: </strong>This study seeks to explore the anti-tumor effect and mechanism of DIOS in cutaneous melanoma.</p><p><strong>Methods: </strong>Here, a variety of in vitro and in vivo experiments, combined with RNA sequencing (RNA-seq), were employed to ascertain the potential anti-cutaneous melanoma capacity and mechanism of DIOS.</p><p><strong>Results: </strong>The results demonstrated that DIOS considerably impeded cell proliferation and triggered cell apoptosis in a dose- and time-dependent manner. Concurrently, DIOS markedly elevated the expression of pro-apoptotic proteins (Cleaved caspase-3, Bax, Cleaved PARP, and Cleaved caspase-9) and downregulated the expression of Bcl-2. Additionally, DIOS markedly upregulated the protein expressions of LC3B-II and Atg5, while downregulating p62 protein expression. Notably, pre-treatment with an autophagy inhibitor significantly inhibited DIOSinduced cell apoptosis and autophagy. Mechanistically, DIOS was identified to repress the PI3K/Akt/mTOR signaling pathway by western blot analyses and RNA-seq. Finally, in vivo experiments using a syngeneic mouse model confirmed the anti-tumor effect of DIOS, which exhibited high levels of apoptosis and autophagy.</p><p><strong>Conclusion: </strong>These findings propose that DIOS acts as a potential melanoma therapy that exerts its anti-tumor effects by triggering apoptosis and autophagy via inhibition of the PI3K/Akt/mTOR pathway.</p>\",\"PeriodicalId\":7934,\"journal\":{\"name\":\"Anti-cancer agents in medicinal chemistry\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":2.6000,\"publicationDate\":\"2025-01-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Anti-cancer agents in medicinal chemistry\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2174/0118715206360266250115065234\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Anti-cancer agents in medicinal chemistry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/0118715206360266250115065234","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Effects of Citrus-derived Diosmetin on Melanoma: Induction of Apoptosis and Autophagy Mediated by PI3K/Akt/mTOR Pathway Inhibition.
Background: Diosmetin (DIOS) is a naturally abundant flavonoid and possesses various biological activities that hold promise as an anti-cancer agent. However, the anti-cancer activities and underlying mechanism of DIOS on cutaneous melanoma remain unclear.
Objective: This study seeks to explore the anti-tumor effect and mechanism of DIOS in cutaneous melanoma.
Methods: Here, a variety of in vitro and in vivo experiments, combined with RNA sequencing (RNA-seq), were employed to ascertain the potential anti-cutaneous melanoma capacity and mechanism of DIOS.
Results: The results demonstrated that DIOS considerably impeded cell proliferation and triggered cell apoptosis in a dose- and time-dependent manner. Concurrently, DIOS markedly elevated the expression of pro-apoptotic proteins (Cleaved caspase-3, Bax, Cleaved PARP, and Cleaved caspase-9) and downregulated the expression of Bcl-2. Additionally, DIOS markedly upregulated the protein expressions of LC3B-II and Atg5, while downregulating p62 protein expression. Notably, pre-treatment with an autophagy inhibitor significantly inhibited DIOSinduced cell apoptosis and autophagy. Mechanistically, DIOS was identified to repress the PI3K/Akt/mTOR signaling pathway by western blot analyses and RNA-seq. Finally, in vivo experiments using a syngeneic mouse model confirmed the anti-tumor effect of DIOS, which exhibited high levels of apoptosis and autophagy.
Conclusion: These findings propose that DIOS acts as a potential melanoma therapy that exerts its anti-tumor effects by triggering apoptosis and autophagy via inhibition of the PI3K/Akt/mTOR pathway.
期刊介绍:
Formerly: Current Medicinal Chemistry - Anti-Cancer Agents.
Anti-Cancer Agents in Medicinal Chemistry aims to cover all the latest and outstanding developments in medicinal chemistry and rational drug design for the discovery of anti-cancer agents.
Each issue contains a series of timely in-depth reviews and guest edited issues written by leaders in the field covering a range of current topics in cancer medicinal chemistry. The journal only considers high quality research papers for publication.
Anti-Cancer Agents in Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments in cancer drug discovery.