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Mechanism of action of the antileukemic xanthone psorospermin: DNA strand breaks, abasic sites, and protein-DNA cross-links.
Cancer Res. 1994 Jun 15; 54(12):3191-5.CR

Abstract

Psorospermin, a cytotoxic dihydrofuranoxanthone isolated from Psorospermum febrifugum, produced aberrant simian virus 40 DNA replication intermediates when added to lytically infected CV-1 monkey kidney cells. The aberrant viral intermediates showed dose-dependent DNA strand breaks and protein-DNA cross-links, as well as decreased electrophoretic mobility. Simian virus 40 DNA from psorospermin-treated cells was shown to contain numerous abasic (apyrimidinic/apurinic) sites. The density of abasic sites was a function of the psorospermin dose. We conclude that psorospermin causes extensive loss of DNA bases in vivo. Primary amine groups of cellular proteins are known to react with abasic sites to form covalent protein-DNA cross-links and DNA strand breaks. Cytochrome c cross-linked spontaneously to viral DNA prepared from psorospermin-treated cells but not to DNA from untreated cells. This suggests that the protein-DNA cross-links and many of the DNA strand breaks observed in vivo result from reactions between abasic sites and chromosomal proteins. It is likely that the protein-DNA cross-links and DNA strand breaks contribute to the cytotoxicity and antineoplastic activity of psorospermin.

Authors+Show Affiliations

Department of Radiology, Ohio State University, Columbus 43210.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

8205539

Citation

Permana, P A., et al. "Mechanism of Action of the Antileukemic Xanthone Psorospermin: DNA Strand Breaks, Abasic Sites, and protein-DNA Cross-links." Cancer Research, vol. 54, no. 12, 1994, pp. 3191-5.
Permana PA, Ho DK, Cassady JM, et al. Mechanism of action of the antileukemic xanthone psorospermin: DNA strand breaks, abasic sites, and protein-DNA cross-links. Cancer Res. 1994;54(12):3191-5.
Permana, P. A., Ho, D. K., Cassady, J. M., & Snapka, R. M. (1994). Mechanism of action of the antileukemic xanthone psorospermin: DNA strand breaks, abasic sites, and protein-DNA cross-links. Cancer Research, 54(12), 3191-5.
Permana PA, et al. Mechanism of Action of the Antileukemic Xanthone Psorospermin: DNA Strand Breaks, Abasic Sites, and protein-DNA Cross-links. Cancer Res. 1994 Jun 15;54(12):3191-5. PubMed PMID: 8205539.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mechanism of action of the antileukemic xanthone psorospermin: DNA strand breaks, abasic sites, and protein-DNA cross-links. AU - Permana,P A, AU - Ho,D K, AU - Cassady,J M, AU - Snapka,R M, PY - 1994/6/15/pubmed PY - 1994/6/15/medline PY - 1994/6/15/entrez SP - 3191 EP - 5 JF - Cancer research JO - Cancer Res VL - 54 IS - 12 N2 - Psorospermin, a cytotoxic dihydrofuranoxanthone isolated from Psorospermum febrifugum, produced aberrant simian virus 40 DNA replication intermediates when added to lytically infected CV-1 monkey kidney cells. The aberrant viral intermediates showed dose-dependent DNA strand breaks and protein-DNA cross-links, as well as decreased electrophoretic mobility. Simian virus 40 DNA from psorospermin-treated cells was shown to contain numerous abasic (apyrimidinic/apurinic) sites. The density of abasic sites was a function of the psorospermin dose. We conclude that psorospermin causes extensive loss of DNA bases in vivo. Primary amine groups of cellular proteins are known to react with abasic sites to form covalent protein-DNA cross-links and DNA strand breaks. Cytochrome c cross-linked spontaneously to viral DNA prepared from psorospermin-treated cells but not to DNA from untreated cells. This suggests that the protein-DNA cross-links and many of the DNA strand breaks observed in vivo result from reactions between abasic sites and chromosomal proteins. It is likely that the protein-DNA cross-links and DNA strand breaks contribute to the cytotoxicity and antineoplastic activity of psorospermin. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/8205539/Mechanism_of_action_of_the_antileukemic_xanthone_psorospermin:_DNA_strand_breaks_abasic_sites_and_protein_DNA_cross_links_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=8205539 DB - PRIME DP - Unbound Medicine ER -