Journal article
5'-methylschweinfurthin G reduces chondrosarcoma tumor growth
Journal of orthopaedic research, Vol.36(4), pp.1283-1293
04/2018
DOI: 10.1002/jor.23753
PMID: 28960476
Abstract
New treatment options are urgently required in the field of chondrosarcoma, particularly of chondrosarcomas with a well-differentiated hyaline cartilage-like extracellular matrix (e.g., collagen II and proteoglycan-rich) phenotype, notoriously resistant to drug penetration, and having potential of progression towards higher grade. We investigated the feasibility of using 5'-methylschweinfurthin G (MeSG) as a tumor suppressor agent in the Swarm rat chondrosarcoma, an intermediate- to high-grade chondrosarcoma model, having a hyaline cartilage-like phenotype. Tumor cell culture studies were performed to identify their proliferative and cytotoxicity sensitivity to MeSG. Tumor burden mice were treated with MeSG and analyzed for tumor growth, morphology and regression. The chondrosarcoma tumor cells had a half maximum cytotoxicity concentration (IC
) of 35 nM MeSG; approximately 300-fold less than freshly isolated rat chondrocytes (IC
of 11 µM). Multiple injections of MeSG (20 mg/kg, body weight) resulted in reduced/eliminated tumor growth over a 17-day period in mice, and an 83% reduction (p = 0.023) in tumor mass. Three out of ten MeSG treated mice had complete elimination of tumor. Tumors of treated mice had a decrease in chondrosarcoma cell proliferation (p = 0.012) and an increase in cell death (p = 0.030) compared with tumors of control mice. These findings in an animal model demonstrate the effectiveness of MeSG for treatment of rat chondrosarcomas, and may have the potential use as a therapeutic option for the difficult-to-treat intermediate-to high-grade hyaline cartilage-like chondrosarcoma. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1283-1293, 2018.
Details
- Title: Subtitle
- 5'-methylschweinfurthin G reduces chondrosarcoma tumor growth
- Creators
- Jeff W Stevens - Department of Internal Medicine, Carver College of Medicine, The University of Iowa, 500 Newton Road, 3160 ML, Iowa City, 52242, IowaDavid K Meyerholz - Department of Pathology, Carver College of Medicine, The University of Iowa, 500 Newton Road, 1165 ML, Iowa City, 52242, IowaJeffery D Neighbors - Departments of Pharmacology and Medicine, Pennsylvania State College of Medicine, Pennsylvania State Cancer Institute, 500 University Drive, CH72, Hershey, 17033, PennsylvaniaJosé A Morcuende - Department of Orthopaedic Surgery, Carver College of Medicine, University of Iowa, 200 Hawkins Drive, 01023 JPP, Iowa City, 52242, Iowa
- Resource Type
- Journal article
- Publication Details
- Journal of orthopaedic research, Vol.36(4), pp.1283-1293
- Publisher
- United States
- DOI
- 10.1002/jor.23753
- PMID
- 28960476
- ISSN
- 0736-0266
- eISSN
- 1554-527X
- Grant note
- DOI: 10.13039/100011343, name: Holden Comprehensive Cancer Center, University of Iowa
- Language
- English
- Date published
- 04/2018
- Academic Unit
- Stead Family Department of Pediatrics; Pathology; Orthopedics and Rehabilitation
- Record Identifier
- 9984040016902771
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