The effect of 9,11-secosterol, a newly discovered compound from the soft coral Gersemia fruticosa, on the growth and cell cycle progression of various tumor cells in culture.
A new 9,11-secosterol, 24-nor-9,11-seco-11-acetoxy-3 beta,6 alpha-dihydroxycholest-7,22(E)-dien-9-one, was found to exhibit growth inhibitory (IC50 below 10 microM) and cytotoxic activities against human leukemia K562, human cervical cancer HeLa, and Ehrlich ascites tumor cells in vitro. The cytostatic concentrations of the compound generally caused the G2/M block in the cell cycle progression, but differences between the three tumor cell lines in the events leading to cell death were remarkable. While inhibiting cell proliferation, 9,11-secosterol caused accumulation of HeLa and K562 cells in the metaphase of mitosis. So, abnormal mitosis can play an important role in the cytotoxicity of 9,11-secosterol in these cell lines. In the Ehrlich ascites tumor cell line the increasing concentrations of the drug (up to 40 microM) did not cause an immediate cell killing. Instead, due to continued DNA synthesis without entry into mitosis, cells with high DNA ploidy were produced. It was shown that the cytoskeletal systems such as microtubules and microfilaments were not damaged by the action of 9,11-secosterol. Further studies are necessary to elucidate the mechanism of the cytotoxic effect of 9,11-secosterol.
Lopp
A
A
Department of Bioorganic Chemistry, Estonian Academy of Sciences, Tallinn.
Pihlak
A
A
Paves
H
H
Samuel
K
K
Koljak
R
R
Samel
N
N
D000818:Animals; D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D002783:Cholestenones / Q000302:isolation & purification / Q000494:pharmacology*; D002877:Chromosomes, Human / Q000187:drug effects; D003063:Cnidaria / Q000737:chemistry*; D006131:Growth Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D008870:Microtubules / Q000187:drug effects; D015394:Molecular Structure; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D002783:Cholestenones; D006131:Growth Inhibitors; C089194:24-nor-9,11-seco-11-acetoxy-3,6-dihydroxycholest-7,22-dien-9-one