Abstract
Purpose. 2-Methoxyestradiol (2ME2), a metabolite of 17β-estradiol, is currently undergoing extensive clinical testing as an antitumor agent. This drug antagonizes both angiogenesis and induces apoptosis in some tumor cell lines. Growth plate alterations as well as an inhibition of longitudinal bone growth have been reported in young rats treated with a pharmacological dose of 2ME2. However, 2ME2's mechanism of action at the growth plate is unknown. To uncover the mechanism, we examined the dose-response effects of 2ME2 on growth plate chondrocytes.
Methods. 2ME2 (4-, 20-, and 75 mg·kg·day) was administered orally to recently ovariectomized 10-week-old rats. The number of cells undergoing DNA synthesis was evaluated with 3H-thymidine radioautography, apoptosis-induced DNA fragmentation was detected with TUNEL assay, and longitudinal growth rates were determined with fluorochrome labeling.
Results. 2ME2 reduced bone elongation (P≤0.05), suppressed chondrocyte proliferation (P≤0.05), and induced chondrocyte apoptosis (P≤0.05). Furthermore, 1-week treatment with 2ME2 did not affect the size of hypertrophic chondrocytes.
Conclusion. Thus, pharmacological doses of 2ME2 utilized for tumor suppression can inhibit normal bone elongation in growing rats by reducing the number of proliferating chondrocytes in the growth plate and accelerating apoptosis in differentiated chondrocytes. This demonstration identifies another organ in which toxicity should potentially be monitored in ongoing and future clinical trials of 2ME2.
Similar content being viewed by others
Author information
Authors and Affiliations
Additional information
Electronic Publication
Rights and permissions
About this article
Cite this article
Sibonga, J.D., Sommer, U. & Turner, R.T. Evidence that 2-methoxyestradiol suppresses proliferation and accelerates apoptosis in normal rat growth plate chondrocytes. J Cancer Res Clin Oncol 128, 477–483 (2002). https://doi.org/10.1007/s00432-002-0367-9
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s00432-002-0367-9