Induction of apoptotic cell death by DNA topoisomerase II inhibitors.
We have analyzed the interference of antitumoral drugs acting through the inhibition of DNA topoisomerase II on the human HeLa cell metabolism. Different compounds characterized by a diverse mechanism of action have been used, namely m-amsacrine, an intercalative drug, etoposide, which does not intercalate DNA, and suramin, which exerts its effect through an unknown mechanism. In HeLa cells treated with increasing doses of these drugs, we have examined cell viability and DNA synthesis capacity, and we have evaluated topoisomerase II activity. Cellular morphology and DNA integrity have been studied in order to characterize the mechanism of cell death. The results we have obtained clearly indicate that topoisomerase II poisons induce cell death by apoptosis. These observations suggest a role of the inhibition of topoisomerase II activity in the apoptotic program.
Negri
C
C
Istituto di Genetica Biochemica Evoluzionistica CNR, Pavia, Italy.
Bernardi
R
R
Donzelli
M
M
Scovassi
A I
AI
D000677:Amsacrine / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols; D017209:Apoptosis / Q000502:physiology*; D002330:Carmustine / Q000494:pharmacology; D002470:Cell Survival; D003520:Cyclophosphamide / Q000494:pharmacology; D004249:DNA Damage; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D005047:Etoposide / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D007364:Intercalating Agents / Q000494:pharmacology*; D013498:Suramin / Q000494:pharmacology*; D059005:Topoisomerase II Inhibitors
D000970:Antineoplastic Agents; D007364:Intercalating Agents; D059005:Topoisomerase II Inhibitors; D000677:Amsacrine; D013498:Suramin; D005047:Etoposide; D003520:Cyclophosphamide; D004250:DNA Topoisomerases, Type II; D002330:Carmustine