@article {Fu677, author = {Qin Fu and Seung-Whan Kim and Hong-Xin Chen and Susan Grill and Yung-Chi Cheng}, title = {Degradation of Topoisomerase I Induced by Topoisomerase I Inhibitors Is Dependent on Inhibitor Structure but Independent of Cell Death}, volume = {55}, number = {4}, pages = {677--683}, year = {1999}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {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}, issn = {0026-895X}, URL = {https://molpharm.aspetjournals.org/content/55/4/677}, eprint = {https://molpharm.aspetjournals.org/content/55/4/677.full.pdf}, journal = {Molecular Pharmacology} }