Antitumor effects of 3,3',4,4',5,5'-hexahydroxystilbene in HL-60 human promyelocytic leukemia cells.
Resveratrol (3,4',5-trihydroxystilbene, RV) exerts remarkable cytostatic and cytotoxic effects against a multitude of human cancer cell lines. Since the introduction of additional hydroxyl groups was supposed to increase the biological activity of RV, we have synthesized a number of polyhydroxylated stilbene analogues as potential antitumor agents. In this study, the activity of 3,3',4,4',5,5'-hexahydroxystilbene (M8) was investigated in HL-60 human promyelocytic leukemia cells. Employing a growth inhibition assay, incubation with M8 and RV resulted in IC50 values of 6.25 and 12 microM, respectively. Using a specific Hoechst/propidium iodide double staining method, we found that M8 was able to induce apoptosis in concentrations significantly lower than those of RV. In addition, M8 arrested cells in the S phase and totally depleted cells in the G2-M phase of the cell cycle (143% and 0% of control after treatment with 12.5 microM M8, respectively). We therefore believe that this promising agent deserves further preclinical and in vivo testing.
Saiko
P
P
Clinical Institute of Medical and Chemical Laboratory Diagnostics, General Hospital of Vienna, Medical University of Vienna, Vienna, Austria. saiko@inode.at
Horvath
Z
Z
Murias
M
M
Handler
N
N
Jaeger
W
W
Erker
T
T
Fritzer-Szekeres
M
M
Szekeres
T
T
D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D006690:Bisbenzimidazole / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D003561:Cytarabine / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D005456:Fluorescent Dyes / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy*; D011419:Propidium / Q000494:pharmacology; D011748:Pyrogallol / Q000031:analogs & derivatives* / Q000494:pharmacology; D013267:Stilbenes / Q000494:pharmacology*
C514772:3,3',4,4',5,5'-hexahydroxystilbene; D000970:Antineoplastic Agents; D005456:Fluorescent Dyes; D013267:Stilbenes; D011748:Pyrogallol; D003561:Cytarabine; D011419:Propidium; D006690:Bisbenzimidazole