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SF2523 inhibits human chondrosarcoma cell growth in vitro and in vivo.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2019 Apr 09; Vol. 511 (3), pp. 559-565. Date of Electronic Publication: 2019 Feb 26. - Publication Year :
- 2019
-
Abstract
- Developing novel therapeutic agents against chondrosarcoma is important. SF2523 is a PI3K-Akt-mTOR and bromodomain-containing protein 4 (BRD4) dual inhibitor. Its activity in human chondrosarcoma cells is tested. Our results show that SF2523 potently inhibited survival, proliferation and migration, and induced apoptosis activation in SW1353 cells and primary human chondrosarcoma cells. The dual inhibitor was yet non-cytotoxic to the primary human osteoblasts and OB-6 osteoblastic cells. SF2523 blocked Akt-mTOR activation and downregulated BRD4-regulated genes (Bcl-2 and c-Myc) in chondrosarcoma cells. It was more efficient in killing chondrosarcoma cells than other established PI3K-Akt-mTOR and BRD4 inhibitors, including JQ1, perifosine and OSI-027. In vivo, intraperitoneal injection of SF2523 (30 mg/kg) potently inhibited subcutaneous SW1353 xenograft tumor growth in severe combined immunodeficient mice. Akt-mTOR inhibition as well as Bcl-2 and c-Myc downregulation were detected in SF2523-treated SW1353 tumor tissues. In conclusion, targeting PI3K-Akt-mTOR and BRD4 by SF2523 potently inhibited chondrosarcoma cell growth in vitro and in vivo.<br /> (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Subjects :
- Adult
Animals
Antineoplastic Agents therapeutic use
Bone Neoplasms metabolism
Bone Neoplasms pathology
Cell Cycle Proteins antagonists & inhibitors
Cell Line, Tumor
Chondrosarcoma metabolism
Chondrosarcoma pathology
Humans
Male
Mice, SCID
Middle Aged
Morpholines therapeutic use
Phosphoinositide-3 Kinase Inhibitors therapeutic use
Proto-Oncogene Proteins c-akt antagonists & inhibitors
Pyrans therapeutic use
TOR Serine-Threonine Kinases antagonists & inhibitors
Transcription Factors antagonists & inhibitors
Antineoplastic Agents pharmacology
Bone Neoplasms drug therapy
Cell Proliferation drug effects
Chondrosarcoma drug therapy
Morpholines pharmacology
Pyrans pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2104
- Volume :
- 511
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 30824188
- Full Text :
- https://doi.org/10.1016/j.bbrc.2019.02.080