Dehydroleucodine induces senescence through the p53 signaling pathway

COSTANTINO V; AMAYA C; LOSINNO AD; LOPEZ LA

Mendoza

Congreso; XLVIII Reunión Anual de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular; 2012

Sociedad Argentina de Investigación Bioquímica

Among antitumor drugs currently studied, the sesquiterpene lactones (SLs) are of particular interest due to its cell antiproliferative activity. Dehydroleucodine (DhL) is a SLpurified from , a medicinal plant used in Argentina. Previous results from our laboratory showed that DhL inhibits the HeLa cells proliferation, arresting them in the G1 cell cycle phase. In this work we asked whether the antiproliferative effect of DhL is related with the induction of senescence and is involved the tumor suppressor p53. HeLa cells were treated with 0-20 μM DhL for 48 h. The cellular senescence was evaluated by the senescence-associated ß-galactosidase (SA-ß-Gal) in situ assays and the levels of p53 and p21 were assayed by Western blot. The treatment with 0 μMDhLinduced 6.60%± 4.30 of cells positive to SA-ß-Gal and with 20 μM DhL, 53.41 % ± 1.51. In addition, the treatment with 20 μM DhLincreased 27.84%± 3.02 and 114.01% ± 19.6 the levels of p53 and p21 respectively. These results indicate that the DhL effect on HeLa cell arrest is due to induction of senescence through the p53-p21 signaling pathway.