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.