Yu Dai , Guan Huang , Xiao Zhong , Yihua Yang , Junqiang Ye
{"title":"N6-(2-羟乙基)-腺苷(HEA)通过调节IGF1信号传导,在骨肉瘤进展中表现出抗肿瘤活性","authors":"Yu Dai , Guan Huang , Xiao Zhong , Yihua Yang , Junqiang Ye","doi":"10.1016/j.fitote.2024.106319","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Osteosarcoma is a highly malignant bone tumor with poor prognosis and limited treatment options due to resistance and side effects.</div></div><div><h3>Objectives</h3><div>This study investigates the effects of N6-(2-hydroxyethyl)-adenosine (HEA) on osteosarcoma cells and its impact on the IGF1 signaling pathway.</div></div><div><h3>Methods</h3><div>Saos2 and MG63 cell lines were treated with HEA. Cell viability, apoptosis, migration, invasion, and EMT markers were assessed. IGF1 expression was analyzed using Western blot, qPCR, and ELISA. IGF1 silencing and recombinant IGF1 treatments were used to explore HEA's mechanisms.</div></div><div><h3>Results</h3><div>HEA significantly decreased osteosarcoma cell viability and induced apoptosis in a dose- and time-dependent manner. It also inhibited cell migration and invasion, and modulated EMT markers by upregulating E-cadherin and downregulating N-cadherin and vimentin. HEA downregulated IGF1 at both the mRNA and protein levels, and reduced IGF1 secretion. Furthermore, HEA inhibited the PI3K-AKT signaling pathway, which is activated by IGF1. IGF1 silencing mimicked HEA's effects, whereas recombinant IGF1 pre-treatment partially reversed HEA's effects on cell viability, apoptosis, and EMT markers.</div></div><div><h3>Conclusions</h3><div>HEA exerts potent anti-cancer effects on osteosarcoma cells both <em>in vitro</em> and <em>in vivo</em> by targeting the IGF1 pathway and inhibiting downstream PI3K-AKT signaling. These results suggest that HEA holds promise as a novel therapeutic agent for osteosarcoma.</div></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":"180 ","pages":"Article 106319"},"PeriodicalIF":2.5000,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"N6-(2-hydroxyethyl)-adenosine (HEA) exhibits antitumor activity for osteosarcoma progression by regulating IGF1 signaling\",\"authors\":\"Yu Dai , Guan Huang , Xiao Zhong , Yihua Yang , Junqiang Ye\",\"doi\":\"10.1016/j.fitote.2024.106319\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>Osteosarcoma is a highly malignant bone tumor with poor prognosis and limited treatment options due to resistance and side effects.</div></div><div><h3>Objectives</h3><div>This study investigates the effects of N6-(2-hydroxyethyl)-adenosine (HEA) on osteosarcoma cells and its impact on the IGF1 signaling pathway.</div></div><div><h3>Methods</h3><div>Saos2 and MG63 cell lines were treated with HEA. Cell viability, apoptosis, migration, invasion, and EMT markers were assessed. IGF1 expression was analyzed using Western blot, qPCR, and ELISA. IGF1 silencing and recombinant IGF1 treatments were used to explore HEA's mechanisms.</div></div><div><h3>Results</h3><div>HEA significantly decreased osteosarcoma cell viability and induced apoptosis in a dose- and time-dependent manner. It also inhibited cell migration and invasion, and modulated EMT markers by upregulating E-cadherin and downregulating N-cadherin and vimentin. HEA downregulated IGF1 at both the mRNA and protein levels, and reduced IGF1 secretion. Furthermore, HEA inhibited the PI3K-AKT signaling pathway, which is activated by IGF1. IGF1 silencing mimicked HEA's effects, whereas recombinant IGF1 pre-treatment partially reversed HEA's effects on cell viability, apoptosis, and EMT markers.</div></div><div><h3>Conclusions</h3><div>HEA exerts potent anti-cancer effects on osteosarcoma cells both <em>in vitro</em> and <em>in vivo</em> by targeting the IGF1 pathway and inhibiting downstream PI3K-AKT signaling. These results suggest that HEA holds promise as a novel therapeutic agent for osteosarcoma.</div></div>\",\"PeriodicalId\":12147,\"journal\":{\"name\":\"Fitoterapia\",\"volume\":\"180 \",\"pages\":\"Article 106319\"},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2024-11-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Fitoterapia\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0367326X24005021\",\"RegionNum\":3,\"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":"Fitoterapia","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0367326X24005021","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
N6-(2-hydroxyethyl)-adenosine (HEA) exhibits antitumor activity for osteosarcoma progression by regulating IGF1 signaling
Background
Osteosarcoma is a highly malignant bone tumor with poor prognosis and limited treatment options due to resistance and side effects.
Objectives
This study investigates the effects of N6-(2-hydroxyethyl)-adenosine (HEA) on osteosarcoma cells and its impact on the IGF1 signaling pathway.
Methods
Saos2 and MG63 cell lines were treated with HEA. Cell viability, apoptosis, migration, invasion, and EMT markers were assessed. IGF1 expression was analyzed using Western blot, qPCR, and ELISA. IGF1 silencing and recombinant IGF1 treatments were used to explore HEA's mechanisms.
Results
HEA significantly decreased osteosarcoma cell viability and induced apoptosis in a dose- and time-dependent manner. It also inhibited cell migration and invasion, and modulated EMT markers by upregulating E-cadherin and downregulating N-cadherin and vimentin. HEA downregulated IGF1 at both the mRNA and protein levels, and reduced IGF1 secretion. Furthermore, HEA inhibited the PI3K-AKT signaling pathway, which is activated by IGF1. IGF1 silencing mimicked HEA's effects, whereas recombinant IGF1 pre-treatment partially reversed HEA's effects on cell viability, apoptosis, and EMT markers.
Conclusions
HEA exerts potent anti-cancer effects on osteosarcoma cells both in vitro and in vivo by targeting the IGF1 pathway and inhibiting downstream PI3K-AKT signaling. These results suggest that HEA holds promise as a novel therapeutic agent for osteosarcoma.
期刊介绍:
Fitoterapia is a Journal dedicated to medicinal plants and to bioactive natural products of plant origin. It publishes original contributions in seven major areas:
1. Characterization of active ingredients of medicinal plants
2. Development of standardization method for bioactive plant extracts and natural products
3. Identification of bioactivity in plant extracts
4. Identification of targets and mechanism of activity of plant extracts
5. Production and genomic characterization of medicinal plants biomass
6. Chemistry and biochemistry of bioactive natural products of plant origin
7. Critical reviews of the historical, clinical and legal status of medicinal plants, and accounts on topical issues.