A plant steroid, diosgenin, induces apoptosis, cell cycle arrest and COX activity in osteosarcoma cells

Cyclooxygenases (COXs) are key enzymes in the conversion of arachidonic aci d into prostanoids. which are involved in apoptosis and inflammation. Two d istinct COXs have been identified: COX-1 which is constitutively expressed and COX-2 which is induced by different products such as tumor promoters or growth factors. Previously, we demonstrated that a plant steroid, diosgeni n, was a new megakaryocytic differentiation inducer of human erythroleukemi a cells. In our study, we investigated the effect of diosgenin on the proli feration rate, cell cycle distribution and apoptosis in the human osteosarc oma 1547 cell line. The effects of this compound were also tested on COX ex pression and COX activities. Diosgenin treatment cause an inhibition of 154 7 cell growth with a cycle arrest in G, phase and apoptosis induction. More over, we found a correlation between p53, p21 mRNA expression and nuclear f actor-KB activation and we observed a time-dependent increase in PGE(2) syn thesis after diosgenin treatment. (C) 2001 Federation of European Biochemic al Societies. Published by Elsevier Science B.V. All rights reserved.