Anticancer activity and possible mode of action of 4-O-podophyllotoxinyl 12-hydroxyl-octadec-Z-9-enoate.
4-O-Podophyllotoxinyl 12-hydroxyl-octadec-Z-9-enoate (PHEFE) is a structurally novel FA analog of podophyllotoxin. In the present study, in vitro effects of PHEFE on a panel of 60 human tumor cell lines and its potential modes of anticancer action were investigated. PHEFE exhibited strong growth-inhibitory action in a number of solid tumor cells in vitro. It did not inhibit tubulin polymerization as podophyllotoxin does; rather, it inhibited the catalytic activity of topoisomerase II. Flow cytometry and staining assay with 4,6-diamidine-2-phenylindole dihydrochloride showed that PHEFE blocked the cell cycle at the G2/M phase and induced apoptosis in HL-60 cells. These analyses suggest that PHEFE has promising anticancer characteristics that differ from podophyllotoxin and etoposide.
Ma
Guoyi
G
National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, University, Mississippi 38677, USA.
Khan
Shabana I
SI
Mustafa
Jamal
J
Walker
Larry A
LA
Khan
Ikhlas A
IA
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects*; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D009829:Oleic Acids / Q000138:chemical synthesis / Q000494:pharmacology*; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D059005:Topoisomerase II Inhibitors
C505095:4-O-podophyllotoxinyl 12-hydroxyl-octadec-Z-9-enoate; D000970:Antineoplastic Agents; D009829:Oleic Acids; D059005:Topoisomerase II Inhibitors; D011034:Podophyllotoxin