Roberta Rocca, Serena Ascrizzi, Emanuele Liborio Citriniti, Francesca Scionti, Giada Juli, Maria Teresa Di Martino, Daniele Caracciolo, Anna Artese, Pierosandro Tagliaferri, Pierfrancesco Tassone, Katia Grillone, Stefano Alcaro
{"title":"抗多发性骨髓瘤活性背后的 TERRA G-四叉链稳定作用:关于白藜芦醇多生物效应的新见解","authors":"Roberta Rocca, Serena Ascrizzi, Emanuele Liborio Citriniti, Francesca Scionti, Giada Juli, Maria Teresa Di Martino, Daniele Caracciolo, Anna Artese, Pierosandro Tagliaferri, Pierfrancesco Tassone, Katia Grillone, Stefano Alcaro","doi":"10.1002/ardp.202400269","DOIUrl":null,"url":null,"abstract":"<p>Resveratrol (RSV) is a nutraceutical compound belonging to the nonflavonoid polyphenol family, whose antioxidants, anti-inflammatory, and antitumoral properties have been widely investigated. The ability of RSV to provide beneficial effects for neurological, cardiovascular, and cancer disorders rekindled the interest to explore the molecular mechanisms behind its pleiotropic effects, which are due to the modulation of coding and noncoding genes involved in many key biological pathways. With a computational approach, including docking studies and thermodynamics calculations followed by 200-ns-long molecular dynamics and a clustering analysis, we hypothesized the stabilizing binding between RSV and G4 structures of telomeric repeat-containing RNA (TERRA), which is a tumor-suppressive long noncoding RNAs (lncRNA) involved in the regulation of telomere maintenance. In vitro studies performed on cellular models of multiple myeloma (MM) strengthened our hypothesis by highlighting that the antiproliferative and apoptotic effect induced by the treatment with RSV is associated with an increase of TERRA transcript and with upregulation of telomeric heterochromatin markers, such as H3K27Me3 and H4K20Me3, and of the hallmark of apoptosis, cleaved-poly(ADP-ribose) polymerase-1. Our results propose innovative insights underlying the multifaceted role of RSV in MM, by pointing out the role of this natural compound in an lncRNA-mediated regulation to counteract cellular immortality.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":null,"pages":null},"PeriodicalIF":4.3000,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"TERRA G-quadruplex stabilization behind the anti-multiple myeloma activity: Novel insights about resveratrol pleiotropic effects\",\"authors\":\"Roberta Rocca, Serena Ascrizzi, Emanuele Liborio Citriniti, Francesca Scionti, Giada Juli, Maria Teresa Di Martino, Daniele Caracciolo, Anna Artese, Pierosandro Tagliaferri, Pierfrancesco Tassone, Katia Grillone, Stefano Alcaro\",\"doi\":\"10.1002/ardp.202400269\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Resveratrol (RSV) is a nutraceutical compound belonging to the nonflavonoid polyphenol family, whose antioxidants, anti-inflammatory, and antitumoral properties have been widely investigated. The ability of RSV to provide beneficial effects for neurological, cardiovascular, and cancer disorders rekindled the interest to explore the molecular mechanisms behind its pleiotropic effects, which are due to the modulation of coding and noncoding genes involved in many key biological pathways. With a computational approach, including docking studies and thermodynamics calculations followed by 200-ns-long molecular dynamics and a clustering analysis, we hypothesized the stabilizing binding between RSV and G4 structures of telomeric repeat-containing RNA (TERRA), which is a tumor-suppressive long noncoding RNAs (lncRNA) involved in the regulation of telomere maintenance. In vitro studies performed on cellular models of multiple myeloma (MM) strengthened our hypothesis by highlighting that the antiproliferative and apoptotic effect induced by the treatment with RSV is associated with an increase of TERRA transcript and with upregulation of telomeric heterochromatin markers, such as H3K27Me3 and H4K20Me3, and of the hallmark of apoptosis, cleaved-poly(ADP-ribose) polymerase-1. Our results propose innovative insights underlying the multifaceted role of RSV in MM, by pointing out the role of this natural compound in an lncRNA-mediated regulation to counteract cellular immortality.</p>\",\"PeriodicalId\":128,\"journal\":{\"name\":\"Archiv der Pharmazie\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.3000,\"publicationDate\":\"2024-06-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Archiv der Pharmazie\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/ardp.202400269\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Archiv der Pharmazie","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/ardp.202400269","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
TERRA G-quadruplex stabilization behind the anti-multiple myeloma activity: Novel insights about resveratrol pleiotropic effects
Resveratrol (RSV) is a nutraceutical compound belonging to the nonflavonoid polyphenol family, whose antioxidants, anti-inflammatory, and antitumoral properties have been widely investigated. The ability of RSV to provide beneficial effects for neurological, cardiovascular, and cancer disorders rekindled the interest to explore the molecular mechanisms behind its pleiotropic effects, which are due to the modulation of coding and noncoding genes involved in many key biological pathways. With a computational approach, including docking studies and thermodynamics calculations followed by 200-ns-long molecular dynamics and a clustering analysis, we hypothesized the stabilizing binding between RSV and G4 structures of telomeric repeat-containing RNA (TERRA), which is a tumor-suppressive long noncoding RNAs (lncRNA) involved in the regulation of telomere maintenance. In vitro studies performed on cellular models of multiple myeloma (MM) strengthened our hypothesis by highlighting that the antiproliferative and apoptotic effect induced by the treatment with RSV is associated with an increase of TERRA transcript and with upregulation of telomeric heterochromatin markers, such as H3K27Me3 and H4K20Me3, and of the hallmark of apoptosis, cleaved-poly(ADP-ribose) polymerase-1. Our results propose innovative insights underlying the multifaceted role of RSV in MM, by pointing out the role of this natural compound in an lncRNA-mediated regulation to counteract cellular immortality.
期刊介绍:
Archiv der Pharmazie - Chemistry in Life Sciences is an international journal devoted to research and development in all fields of pharmaceutical and medicinal chemistry. Emphasis is put on papers combining synthetic organic chemistry, structural biology, molecular modelling, bioorganic chemistry, natural products chemistry, biochemistry or analytical methods with pharmaceutical or medicinal aspects such as biological activity. The focus of this journal is put on original research papers, but other scientifically valuable contributions (e.g. reviews, minireviews, highlights, symposia contributions, discussions, and essays) are also welcome.