title: Cytotoxic and apoptosis-inducing effect of ent-15-oxo-kaur-16-en-19-oic acid, a derivative of grandiflorolic acid from Espeletia schultzii.
abstract: ent-Kaurenic acid and many natural derivatives of this diterpene are known to have interesting biological properties. ent-15-Oxo-kaur-16-en-19-oic acid can be easily obtained from grandiflorolic acid which was first isolated from Espeletia grandiflora. The present work describes the proapoptotic effect of ent-15-oxo-kaur-16-en-19-oic acid on the human prostate carcinoma epithelial cell line PC-3 as evidenced by the changes in the expression level of proteins associated with the execution and regulation of apoptosis. Cell viability was affected upon exposure to the compound, the IC(50) were determined as 3.7 microg/ml, which is 4 times lower than that corresponding to a primary cell culture of fibroblasts (14.8 microg/mL). Through Western blot analysis, active forms of caspace-3 associated with the specific proteolysis of Poly(ADP-ribose) polymerase (PARP) were detected. Reduced levels of the antiapoptotic protein Bcl-2, as well as the appearance of internucleosomal DNA fragmentation, were also demonstrated. Thus, ent-15-oxo-kaur-16-en-19-oic acid may be a promising lead compound for new chemopreventive strategies, alone or in combination with traditional chemotherapy agents to overcome drug resistance in tumoral cells.
authors.affiliation: Laboratorio de Genómica y Proteómica, Centro de Biotecnología, Fundación IDEA, Carretera Nacional Hoyo de la Puerta-Baruta, Valle de Sartenejas, Municipio Baruta, Edo. Miranda, Caracas 1015-A, Venezuela.
authors.forename: Yarimar
authors.initials: Y
authors.lastname: Ruiz
authors.forename: Juan
authors.initials: J
authors.lastname: Rodrígues
authors.forename: Francisco
authors.initials: F
authors.lastname: Arvelo
authors.forename: Alfredo
authors.initials: A
authors.lastname: Usubillaga
authors.forename: Mariugenia
authors.initials: M
authors.lastname: Monsalve
authors.forename: Nardy
authors.initials: N
authors.lastname: Diez
authors.forename: Iván
authors.initials: I
authors.lastname: Galindo-Castro
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D019659:Asteraceae / Q000737:chemistry*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004224:Diterpenes / Q000737:chemistry / Q000633:toxicity*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D015394:Molecular Structure; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism
chemical_list: D004224:Diterpenes; D019253:Proto-Oncogene Proteins c-bcl-2; C528607:ent-15-oxo-kaur-16-en-19-oic acid; C528608:grandiflorolic acid; D053148:Caspase 3