5′-methylschweinfurthin G reduces chondrosarcoma tumor growth

Jeff W. Stevens, David K. Meyerholz, Jeffery D. Neighbors, José A. Morcuende

Research output: Contribution to journalArticle

2 Citations (Scopus)

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 50 ) of 35 nM MeSG; approximately 300-fold less than freshly isolated rat chondrocytes (IC 50 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.

Original languageEnglish (US)
Pages (from-to)1283-1293
Number of pages11
JournalJournal of Orthopaedic Research
Volume36
Issue number4
DOIs
StatePublished - Apr 2018

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Chondrosarcoma
Growth
Hyaline Cartilage
Neoplasms
Phenotype
5'-methylschweinfurthin G
Proteoglycans
Chondrocytes
Tumor Burden
Extracellular Matrix
Cell Death
Collagen
Therapeutics
Animal Models
Cell Culture Techniques
Body Weight
Cell Proliferation
Injections

All Science Journal Classification (ASJC) codes

  • Orthopedics and Sports Medicine

Cite this

Stevens, Jeff W. ; Meyerholz, David K. ; Neighbors, Jeffery D. ; Morcuende, José A. / 5′-methylschweinfurthin G reduces chondrosarcoma tumor growth. In: Journal of Orthopaedic Research. 2018 ; Vol. 36, No. 4. pp. 1283-1293.
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5′-methylschweinfurthin G reduces chondrosarcoma tumor growth. / Stevens, Jeff W.; Meyerholz, David K.; Neighbors, Jeffery D.; Morcuende, José A.

In: Journal of Orthopaedic Research, Vol. 36, No. 4, 04.2018, p. 1283-1293.

Research output: Contribution to journalArticle

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