Different contribution of apoptosis to the antiproliferative effects of diosgenin and other plant steroids, hecogenin and tigogenin, on human 1547 osteosarcoma cells.
Regulation of growth arrest and apoptosis are, in part, controlled by the tumor suppressor p53 after its phosphorylation which causes a determinant role in its functional activation. Moreover, PPAR regulate many functions such as proliferation and apoptosis. We compared the biological activity of diosgenin with hecogenin and tigogenin, plant steroids structurally close to diosgenin, on proliferation rate, cell cycle distribution and apoptosis in human 1547 osteosarcoma cells. We found that all three molecules have an antiproliferative effect but gel shift analysis demonstrated that none of the plant steroids transactivated PPAR in human 1547 osteosarcoma cells whereas these molecules induced NF-kappaB binding to DNA. Although these plant steroids have a very close structure, only diosgenin caused a cell cycle arrest associated with strong apoptosis. This biological action seems correlated with a large increase of p53 protein expression. This fact was showed by immunofluorescence analysis which confirmed that diosgenin strongly enhanced the activation of p53 in contrast to hecogenin and tigogenin actions.
Corbiere
Cecile
C
Laboratoire de Biochimie, UPRES EA 1085, Faculté de Pharmacie, 87025 Limoges Cedex, France.
Liagre
Bertrand
B
Bianchi
Arnaud
A
Bordji
Karim
K
Dauça
Michel
M
Netter
Patrick
P
Beneytout
Jean-Louis
JL
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D015153:Blotting, Western; D002453:Cell Cycle; D002455:Cell Division; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D004144:Diosgenin / Q000494:pharmacology*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008956:Models, Chemical; D012516:Osteosarcoma / Q000188:drug therapy*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012502:Sapogenins / Q000494:pharmacology*; D013150:Spirostans / Q000494:pharmacology*; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D000970:Antineoplastic Agents; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004365:Drugs, Chinese Herbal; D018160:Receptors, Cytoplasmic and Nuclear; D012502:Sapogenins; D013150:Spirostans; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C007908:hecogenin; C046297:sarsasapogenin; D008156:Luciferases; D004144:Diosgenin