Phenylbenzopyrones structure-activity studies identify betuletol derivatives as potential antitumoral agents.
We have analyzed the cytotoxicity of 22 compounds with a phenylbenzo-gamma-pirone core structure, most of them obtained from natural sources, in five human tumor cell lines (HL-60, A431, SK-OV-3, HeLa and HOS). Betuletol 3-methyl ether and its diacetate were the most cytotoxic compounds. The HL-60 cell line was especially sensitive to these compounds, with IC50 values of approximately 1 microM. Treatment of HL-60 cells with betuletol 3-methyl ether was associated with apoptosis induction which was prevented by a non-specific caspase inhibitor (z-VAD-fmk) and also by a specific inhibitor of caspase-8 (z-IETD-fmk) indicating activation of the extrinsic apoptotic pathway. The results suggest that betuletol 3-methyl ether has potential as new anticancer agent.
Rubio
Sara
S
Department of Biochemistry, I.C.I.C., University of Las Palmas de Gran Canaria, Plaza Dr. Pasteur s/n, 35016 Las Palmas de Gran Canaria, Spain.
Quintana
José
J
López
Mariana
M
Eiroa
José Luis
JL
Triana
Jorge
J
Estévez
Francisco
F
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation; D004987:Ethers / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D004987:Ethers; D005419:Flavonoids; C515374:betuletol 3-methyl ether; D045304:Cytochromes c; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases