| Title: |
MS−275 (Entinostat) promotes radio-sensitivity in PAX3-FOXO1 rhabdomyosarcoma cells |
| Authors: |
Cassandri M.; Pomella S.; Rossetti A.; Petragnano F.; Milazzo L.; Vulcano F.; Camero S.; Codenotti S.; Cicchetti F.; Maggio R.; Festuccia C.; Gravina G. L.; Fanzani A.; Megiorni F.; Catanoso M.; Marchese C.; Tombolini V.; Locatelli F.; Rota R.; Marampon F. |
| Contributors: |
Cassandri, M.; Pomella, S.; Rossetti, A.; Petragnano, F.; Milazzo, L.; Vulcano, F.; Camero, S.; Codenotti, S.; Cicchetti, F.; Maggio, R.; Festuccia, C.; Gravina, G. L.; Fanzani, A.; Megiorni, F.; Catanoso, M.; Marchese, C.; Tombolini, V.; Locatelli, F.; Rota, R.; Marampon, F. |
| Publisher Information: |
MDPI AG; Basel, 4052 Svizzera |
| Publication Year: |
2021 |
| Collection: |
Sapienza Università di Roma: CINECA IRIS |
| Subject Terms: |
DNA damage; HDAC; MS−275; pediatric cancer; radiotherapy; rhabdomyosarcoma; soft tissue sarcoma; animal; apoptosi; benzamide; cell cycle checkpoint; cell line; tumor; cell proliferation; DNA repair; dose-response relationship; drug; gene expression regulation; neoplastic; human; mice; oncogene proteins; fusion; paired box transcription factor; pyridine; Radiation Tolerance; Radiation-Sensitizing Agent |
| Description: |
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood. About 25% of RMS expresses fusion oncoproteins such as PAX3/PAX7-FOXO1 (fusion-positive, FP) while fusion-negative (FN)-RMS harbors RAS mutations. Radiotherapy (RT) plays a crucial role in local control but metastatic RMS is often radio-resistant. HDAC inhibitors (HDACi) radio-sensitize different cancer cells types. Thus, we evaluated MS−275 (Entinostat), a Class I and IV HDACi, in combination with RT on RMS cells in vitro and in vivo. MS−275 reversibly hampered cell survival in vitro in FN-RMS RD (RASmut) and irreversibly in FP-RMS RH30 cell lines down-regulating cyclin A, B, and D1, up-regulating p21 and p27 and reducing ERKs activity, and c-Myc expression in RD and PI3K/Akt/mTOR activity and N-Myc expression in RH30 cells. Further, MS−275 and RT combination reduced colony formation ability of RH30 cells. In both cell lines, co-treatment increased DNA damage repair inhibition and reactive oxygen species formation, down-regulated NRF2, SOD, CAT and GPx4 anti-oxidant genes and improved RT ability to induce G2 growth arrest. MS−275 inhibited in vivo growth of RH30 cells and completely prevented the growth of RTunresponsive RH30 xenografts when combined with radiation. Thus, MS−275 could be considered as a radio-sensitizing agent for the treatment of intrinsically radio-resistant PAX3-FOXO1 RMS. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/34639012; info:eu-repo/semantics/altIdentifier/wos/WOS:000709449500001; volume:22; issue:19; journal:INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; http://hdl.handle.net/11573/1619373 |
| DOI: |
10.3390/ijms221910671 |
| Availability: |
http://hdl.handle.net/11573/1619373; https://doi.org/10.3390/ijms221910671 |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.80B33F23 |
| Database: |
BASE |