This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zwelling, L. A. Articles by Zipf, T. F. Search for Related Content PubMed PubMed Citation Articles by Zwelling, L. A. Articles by Zipf, T. F.

Phorbol Ester Effects on Topoisomerase II Activity and Gene Expression in HL-60 Human Leukemia Cells with Different Proclivities toward Monocytoid Differentiation¹

Departments of Medical Oncology [L. A. Z., M. H., D. C., E. A., J. M.] and Experimental Pediatrics [T. F. Z.], The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030

We examined the effects of phorbol ester treatment on topoisomerase II-mediated events in two human leukemia cell lines with different proclivities toward phorbol ester-induced monocytoid differentiation. HL-60 is the parent line that will terminally differentiate; 1E3 is a derived line that will not terminally differentiate. Within 24 h of phorbol ester treatment, etoposide-induced, topoisomerase II-mediated DNA cleavage declined 10-fold, whereas 4'-(9-acridinylamino)-methanesulfon-m-anisidide-induced DNA cleavage declined 3-fold in HL-60. In phorbol-treated 1E3, etoposide-induced DNA cleavage declined only 2-fold, whereas 4'-(9-acridinylamino)methanesulfon-m-anisidide-induced cleavage was barely affected. There was a 2- to 3-fold decline in topoisomerase II activity within the nuclear extracts from phorbol-treated HL-60 cells but not from phorbol-treated 1E3 cells. Immunoblotting experiments with anti-topoisomerase II antibodies indicated that phorbol treatment produced a structural change in the immunoreactive topoisomerase II in HL-60 nuclear extracts but produced no change in 1E3 topoisomerase II. Phorbol ester treatment also produced a decline in the level of topoisomerase II gene expression in HL-60 but not in 1E3 cells. By contrast, the cytotoxicity of etoposide in both lines was decreased following phorbol treatment. Thus, phorbols may uncouple the mechanisms linking drug-induced, topoisomerase II-DNA cleavable complex stabilization with drug-induced cytotoxicity, particularly in 1E3.

¹ This study was supported by USPHS Research Grants CA40090 (L. A. Z.) and CA39809 (to Dr. Emil J Freireich), Grant CH-324C from the American Cancer Society (L. A. Z.), a grant from the Dunn Foundation (to Dr. Emil J Freireich), and a gift to the M. D. Anderson Annual Fund for the Chemotherapy Research Program from Henry C. Beck, Jr., of Dallas, TX.

² To whom requests for reprints should be addressed, at Box 52, 1515 Holcombe Boulevard, Houston, TX 77030.

Received 4/27/90. Accepted 8/14/90.

This article has been cited by other articles:

				M. Colozza, E. Azambuja, F. Cardoso, C. Sotiriou, D. Larsimont, and M. J. Piccart Proliferative markers as prognostic and predictive tools in early breast cancer: where are we now? Ann. Onc., November 1, 2005; 16(11): 1723 - 1739. [Abstract] [Full Text] [PDF]