Cytotoxic compounds from Annonaceus species as DNA topoisomerase I poisons.
BACKGROUND
In the search for cytotoxic natural products as DNA topoisomerase poisons, we have assessed six annonaceus compounds (the acetogenins annonacin and rolliniastatin-1, the styryl-lactones etharversin and altholactone and the alkaloids thaligrisine and cepharanone-B) for cytotoxic activity against three human cancer cell lines and then we evaluated these compounds as DNA topoisomerase poisons.


METHODS
The cytotoxicity parameters were determined following protocols established by the National Cancer Institute (NCI) using the SRB assay. In the topoisomerase assay, the supercoiled DNA produces open circle forms that are stabilised in the presence of DNA topoisomerase poisons and can be detected after a denaturation step by proteinase K-SDS.


RESULTS
The six compounds showed cytotoxic activity, with cepharanone B being the most cytotoxic one, even more than the antineoplastic agent etoposide on two cancer cell lines, although it is the only one that does not act as a DNA topoisomerase poison.


CONCLUSIONS
These results could justify the traditional use of the studied annonaceus species and topoisomerase-mediated DNA damage might be a possible mechanism by which five of these compounds exert their cytotoxicity.
López-Lázaro
M
M
Departamento de Farmacología, Facultad de Farmacia, Universidad de Sevilla, Spain.
Martín-Cordero
C
C
Bermejo
A
A
Cortes
D
D
Ayuso
M J
MJ
D029061:Annonaceae / Q000737:chemistry*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002460:Cell Line; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D010936:Plant Extracts / Q000494:pharmacology; D059004:Topoisomerase I Inhibitors
D000972:Antineoplastic Agents, Phytogenic; D004791:Enzyme Inhibitors; D010936:Plant Extracts; D059004:Topoisomerase I Inhibitors