Topoisomerase II-dependent novel antitumor compounds merocil and merodantoin induce apoptosis in Daudi cells.
Three photoproducts of merocyanine 540 have been isolated, chemically characterized and synthesized. Two of these photoproducts, merocil and merodantoin, show significant antitumor activity in vitro and in vivo while demonstrating minimal toxicity to normal cells and tissues. Treatment of lymphoma cells with these compounds resulted in a rapid decline in macromolecular synthesis, DNA fragmentation inhibitable by actinomycin D and cycloheximide, and a marked rise in intracellular calcium. In vitro analysis revealed that activity of these compounds is dependent on topoisomerase II. These results are discussed in terms of the novel class of topoisomerase II-dependent compounds for potential use in chemotherapy.
Gulliya
K S
KS
Baylor Research Institute, Dallas, TX 75226.
Franck
B
B
Schneider
U
U
Sharma
R
R
Arnold
L
L
Matthews
J L
JL
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001583:Benzoxazoles / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D004249:DNA Damage; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004273:DNA, Neoplasm / Q000032:analysis / Q000096:biosynthesis; D004587:Electrophoresis, Agar Gel; D005031:Ethylenethiourea / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy; D009363:Neoplasm Proteins / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D013858:Thiobarbiturates / Q000494:pharmacology*; D059005:Topoisomerase II Inhibitors; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D001583:Benzoxazoles; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D013858:Thiobarbiturates; D059005:Topoisomerase II Inhibitors; C092109:meroxazole; C092110:merocil; C089291:merodantoin; D005031:Ethylenethiourea; D004250:DNA Topoisomerases, Type II; D002118:Calcium