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 acid into prostanoids. which are involved in apoptosis and inflammation. Two distinct 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, diosgenin, was a new megakaryocytic differentiation inducer of human erythroleukemia cells. In our study, we investigated the effect of diosgenin on the proliferation rate, cell cycle distribution and apoptosis in the human osteosarcoma 1547 cell line. The effects of this compound were also tested on COX expression and COX activities. Diosgenin treatment cause an inhibition of 1547 cell growth with a cycle arrest in G, phase and apoptosis induction. Moreover, we found a correlation between p53, p21 mRNA expression and nuclear factor-KB activation and we observed a time-dependent increase in PGE(2) synthesis after diosgenin treatment. (C) 2001 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.