The DOI matches its Crossref record.
Effect of VP-16-213 on the intracellular degradation of DNA in HeLa cells
Abstract
The effect of VP-16-213 on cellular DNA was studied by following the sedimentation profiles of radioactive DNA in HeLa cells on alkaline sucrose gradients. In VP-16-213 treated cells, high-molecular-weight DNA is converted to a lower molecular-weight form in a dose-dependent, temperature-dependent reaction. The effect of VP-16-213 on cellular DNA is reversed after the drug has been removed from the growth medium for 150 min. These results suggest that VP-16-213 induces single-stranded breaks in DNA in HeLa cells and that HeLa cells can repair these breaks within 150 min. The nonglucoside derivative of VP-16-213, 4'-demethylepipodophyllotoxin, also induces the cleavage of cellular DNA but podophyllotoxin has no effect on DNA. A structure-activity relationship study, in which the effects of various VP-16-213 and podophyllotoxin congeners were tested for their ability to cleave cellular DNA,revealed that an hydroxyl group at the C-4' position is required for activity and that the configuration of the C-4 carbon influences the activity of a congener. These results may offer insights into the mechanism of action of VP-16-213 as an antitumor agent.
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Citations
Cited by
Tewey, K. M., Chen, G. L., Nelson, E. M., & Liu, L. F. (1984) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)47282-6 · Cited by 887
Teicher, B. A. (1994) · Cancer and Metastasis Reviews · doi:10.1007/bf00689633 · Cited by 563
Topoisomerase-targeting antitumor drugs
D'Arpa, P., & Liu, L. F. (1989) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/0304-419x(89)90041-3 · Cited by 434
Etoposide (VP-16–213): Current Status of an Active Anticancer Drug
O'Dwyer, P. J., Leyland-Jones, B., Alonso, M. T., Marsoni, S., & Wittes, R. E. (1985) · New England Journal of Medicine · doi:10.1056/nejm198503143121106 · Cited by 358
Metadata
- Authors
- Loike, J. D., & Horwitz, S. B.
- Venue
- Biochemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 1976-12
- Volume
- 15
- Issue
- 25
- Pages
- 5443-5448
- ISSN
- 0006-2960 (ISSN-L)
- 1520-4995
- OpenAlex
- W2073983482
- Cited by
- 193
- References
- 0
- FWCI
- 1.06
- Type
- journal article
- Language
- en
- Open access
- closed
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- Loike, J. D., & Horwitz, S. B. (1976). Effect of VP-16-213 on the intracellular degradation of DNA in HeLa cells. Biochemistry. https://doi.org/10.1021/bi00670a004
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