Cytotoxic activity and antiproliferative effects of a new semi-synthetic derivative of Ent-3 beta-hydroxy-13-epi-manoyl oxide on human leukemic cell lines.
Ent-3 beta-hydroxy-13-epi-manoyl oxide (1), was converted to its thiomidazolide derivative (2) which was tested for its cytotoxic activity against a panel of established human leukemic cell lines. Compound 2, exhibited cytotoxic activity against 13 of the cell lines tested. Additionally, compound 2 was examined for its effect on the uptake of [3H]-thymidine as a marker of DNA synthesis and on cell proliferation. The morphology of the cells and the kind of death induced, was investigated. Flow cytometry experiments on a leukemic cell line was also performed. The results show that the semi-synthetic compound, showed a significant antiproliferative effect and kills cells through the process of apoptosis. The appearance of the apoptotic signs was time and dose dependent. From the flow cytometry experiments, a synchronisation through a delay of the cells in G0/1, phase seems to take place.
Dimas
K
K
Hellenic Anticancer Institute, Department of Immunology, Athens, Greece.
Demetzos
C
C
Mitaku
S
S
Vaos
B
B
Marselos
M
M
Tzavaras
T
T
Kokkinopoulos
D
D
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004249:DNA Damage; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004224:Diterpenes / Q000737:chemistry* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005047:Etoposide / Q000494:pharmacology; D005434:Flow Cytometry; D018922:HL-60 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D007938:Leukemia / Q000473:pathology*; D012997:Solvents / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D004224:Diterpenes; D012997:Solvents; C403963:ent-3 beta-hydroxy-13-epi-manoyl oxide; D005047:Etoposide; D004121:Dimethyl Sulfoxide