PT  - JOURNAL ARTICLE
AU  - Qin Fu
AU  - Seung-Whan Kim
AU  - Hong-Xin Chen
AU  - Susan Grill
AU  - Yung-Chi Cheng
TI  - Degradation of Topoisomerase I Induced by Topoisomerase I Inhibitors Is Dependent on Inhibitor Structure but Independent of Cell Death
DP  - 1999 Apr 01
TA  - Molecular Pharmacology
PG  - 677--683
VI  - 55
IP  - 4
4099  - http://molpharm.aspetjournals.org/content/55/4/677.short
4100  - http://molpharm.aspetjournals.org/content/55/4/677.full
SO  - Mol Pharmacol1999 Apr 01; 55
AB  - DNA topoisomerase I (top I) is the target of the antitumor drug camptothecin (CPT) and its analogs. CPT induces dose- and time-dependent degradation of top I. Degradation of top I also occurs in a CPT-resistant cell line and, therefore, is not a consequence of cell death. Top I degradation is preceded by the appearance of a high molecular weight ladder of top I immunoreactivity and can be blocked by specific inhibitors of the proteasome. We compared the effects of five top I poisons [CPT, topotecan, 6-N-formylamino-12,13-dihydro-1,11-dihydroxy-13-(β-d-glucopyranosyl)-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H)-dione (NB506), camptothecin-(para)-4β-amino-4′-O-demethyl Epipodophyllotoxin (W1), and camptothecin-(ortho)-4β-amino-4′-O-demethyl Epipodophyllotoxin (W2)] on cleavable complex formation and top I degradation. Although all five drugs induced cleavable complex formation, two of the drugs, NB506 and W1 did not induce top I degradation. The American Society for Pharmacology and Experimental Therapeutics