Tanshinol suppresses osteosarcoma by specifically inducing apoptosis of U2-OS cells through p53-mediated mechanism
- Publication type:
- Journal article
- Metadata:
-
- Autoren
- Shihui Yu
- Le Guo
- Bo Yan
- Qiang Yuan
- Letian Shan
- Li Zhou
- Thomas Efferth
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000793124100003&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.1016/j.jep.2022.115214
- eISSN
- 1872-7573
- Externe Identifier
- Clarivate Analytics Document Solution ID: 1C4XN
- PubMed Identifier: 35331874
- ISSN
- 0378-8741
- Zeitschrift
- JOURNAL OF ETHNOPHARMACOLOGY
- Schlüsselwörter
- Radix Salviae miltiorrhizae
- Osteosarcoma
- Tanshinol
- Zebrafish
- U2-OS
- MG-63
- Artikelnummer
- ARTN 115214
- Datum der Veröffentlichung
- 2022
- Status
- Published
- Titel
- Tanshinol suppresses osteosarcoma by specifically inducing apoptosis of U2-OS cells through p53-mediated mechanism
- Sub types
- Article
- Ausgabe der Zeitschrift
- 292
Data source: Web of Science (Lite)
- Other metadata sources:
-
- Autoren
- Shihui Yu
- Le Guo
- Bo Yan
- Qiang Yuan
- Letian Shan
- Li Zhou
- Thomas Efferth
- DOI
- 10.1016/j.jep.2022.115214
- ISSN
- 0378-8741
- Zeitschrift
- Journal of Ethnopharmacology
- Sprache
- en
- Artikelnummer
- 115214
- Paginierung
- 115214 - 115214
- Datum der Veröffentlichung
- 2022
- Status
- Published
- Herausgeber
- Elsevier BV
- Herausgeber URL
- http://dx.doi.org/10.1016/j.jep.2022.115214
- Datum der Datenerfassung
- 2023
- Titel
- Tanshinol suppresses osteosarcoma by specifically inducing apoptosis of U2-OS cells through p53-mediated mechanism
- Ausgabe der Zeitschrift
- 292
Data source: Crossref
- Abstract
- <h4>Ethnopharmacological relevance</h4>Radix Salviae miltiorrhizae (also called Danshen in traditional Chinese medicine) is a famous herbal medicine, which has been frequently used to treat blood stasis syndrome including osteosarcoma (OS) in traditional Chinese medicine. Main components of Danshen have been assumed to exhibit anti-OS capacity. Nevertheless, tanshinol (TS, main component of Danshen)'s efficacy and mechanism in OS hasn't been clearly described ever since. This drew our attention, since OS is the most frequent primary bone carcinomas in children and adolescents, with a high incidence and fatality rate. Unfortunately, chemotherapy for OS has faced many clinical challenges due to the increasing chemoresistance and recurrence. This study was then designed to deeply explore TS's role in OS therapy.<h4>Aim of the study</h4>To explore the anti-OS efficacy and mechanism of TS, we conducted in vivo and in vitro experiments by using a zebrafish xenograft model and U2-OS cells.<h4>Materials and methods</h4>CCK-8 assay, DAPI and γ-H2A.X immunofluorescence staining, and flow cytometry (apoptosis verification) were employed to determine the anti-proliferative and pro-apoptotic effects of TS. qPCR and Western blot were used to examine TS's molecular actions and mechanism on apoptosis of U2-OS cells.<h4>Results</h4>The in vivo data showed that TS significantly inhibited U2-OS tumor growth in larval zebrafish from 2 to 20 ng/mL. In vitro data indicated that TS exerted significant anti-proliferative and pro-apoptotic effects on U2-OS cells in a dose-dependent manner. Moreover, TS has no inhibitory effect on bMSCs, suggesting its safety on normal bone-forming cells. Molecular data illustrated that TS obviously activated the p53 signaling-related proteins (p-p53, Bax, CASP3, CASP9) and its upstream JNK (p-JNK, p-c-JUN) and ATM (p-ATM) signaling molecules through phosphorylation and cleavage, followed by up-regulation of the pro-apoptotic genes, NOXA, PUMA, TP53, BAX, and BIM, and down-regulation of Bcl-2 protein.<h4>Conclusion</h4>In sum, TS specifically induced apoptosis of U2-OS cells by activating p53 signaling pathways, indicating TS as a promising candidate for OS treatment.
- Addresses
- College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China; The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
- Autoren
- Shihui Yu
- Le Guo
- Bo Yan
- Qiang Yuan
- Letian Shan
- Li Zhou
- Thomas Efferth
- DOI
- 10.1016/j.jep.2022.115214
- eISSN
- 1872-7573
- Externe Identifier
- PubMed Identifier: 35331874
- Open access
- false
- ISSN
- 0378-8741
- Zeitschrift
- Journal of ethnopharmacology
- Schlüsselwörter
- Cell Line, Tumor
- Animals
- Zebrafish
- Humans
- Salvia miltiorrhiza
- Osteosarcoma
- Bone Neoplasms
- Caffeic Acids
- Apoptosis
- Cell Proliferation
- Adolescent
- Tumor Suppressor Protein p53
- bcl-2-Associated X Protein
- Sprache
- eng
- Medium
- Print-Electronic
- Online publication date
- 2022
- Paginierung
- 115214
- Datum der Veröffentlichung
- 2022
- Status
- Published
- Datum der Datenerfassung
- 2022
- Titel
- Tanshinol suppresses osteosarcoma by specifically inducing apoptosis of U2-OS cells through p53-mediated mechanism.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 292
Data source: Europe PubMed Central
- Abstract
- ETHNOPHARMACOLOGICAL RELEVANCE: Radix Salviae miltiorrhizae (also called Danshen in traditional Chinese medicine) is a famous herbal medicine, which has been frequently used to treat blood stasis syndrome including osteosarcoma (OS) in traditional Chinese medicine. Main components of Danshen have been assumed to exhibit anti-OS capacity. Nevertheless, tanshinol (TS, main component of Danshen)'s efficacy and mechanism in OS hasn't been clearly described ever since. This drew our attention, since OS is the most frequent primary bone carcinomas in children and adolescents, with a high incidence and fatality rate. Unfortunately, chemotherapy for OS has faced many clinical challenges due to the increasing chemoresistance and recurrence. This study was then designed to deeply explore TS's role in OS therapy. AIM OF THE STUDY: To explore the anti-OS efficacy and mechanism of TS, we conducted in vivo and in vitro experiments by using a zebrafish xenograft model and U2-OS cells. MATERIALS AND METHODS: CCK-8 assay, DAPI and γ-H2A.X immunofluorescence staining, and flow cytometry (apoptosis verification) were employed to determine the anti-proliferative and pro-apoptotic effects of TS. qPCR and Western blot were used to examine TS's molecular actions and mechanism on apoptosis of U2-OS cells. RESULTS: The in vivo data showed that TS significantly inhibited U2-OS tumor growth in larval zebrafish from 2 to 20 ng/mL. In vitro data indicated that TS exerted significant anti-proliferative and pro-apoptotic effects on U2-OS cells in a dose-dependent manner. Moreover, TS has no inhibitory effect on bMSCs, suggesting its safety on normal bone-forming cells. Molecular data illustrated that TS obviously activated the p53 signaling-related proteins (p-p53, Bax, CASP3, CASP9) and its upstream JNK (p-JNK, p-c-JUN) and ATM (p-ATM) signaling molecules through phosphorylation and cleavage, followed by up-regulation of the pro-apoptotic genes, NOXA, PUMA, TP53, BAX, and BIM, and down-regulation of Bcl-2 protein. CONCLUSION: In sum, TS specifically induced apoptosis of U2-OS cells by activating p53 signaling pathways, indicating TS as a promising candidate for OS treatment.
- Date of acceptance
- 2022
- Autoren
- Shihui Yu
- Le Guo
- Bo Yan
- Qiang Yuan
- Letian Shan
- Li Zhou
- Thomas Efferth
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/35331874
- DOI
- 10.1016/j.jep.2022.115214
- eISSN
- 1872-7573
- Zeitschrift
- J Ethnopharmacol
- Schlüsselwörter
- MG-63
- Osteosarcoma
- Radix Salviae miltiorrhizae
- Tanshinol
- U2-OS
- Zebrafish
- Adolescent
- Animals
- Apoptosis
- Bone Neoplasms
- Caffeic Acids
- Cell Line, Tumor
- Cell Proliferation
- Humans
- Osteosarcoma
- Salvia miltiorrhiza
- Tumor Suppressor Protein p53
- Zebrafish
- bcl-2-Associated X Protein
- Sprache
- eng
- Country
- Ireland
- Paginierung
- 115214
- PII
- S0378-8741(22)00253-7
- Datum der Veröffentlichung
- 2022
- Status
- Published
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2022
- Titel
- Tanshinol suppresses osteosarcoma by specifically inducing apoptosis of U2-OS cells through p53-mediated mechanism.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 292
Data source: PubMed
- Beziehungen:
- Property of