title: Phytometabolite Dehydroleucodine Induces Cell Cycle Arrest, Apoptosis, and DNA Damage in Human Astrocytoma Cells through p73/p53 Regulation.
abstract: Accumulating evidence supports the idea that secondary metabolites obtained from medicinal plants (phytometabolites) may be important contributors in the development of new chemotherapeutic agents to reduce the occurrence or recurrence of cancer. Our study focused on Dehydroleucodine (DhL), a sesquiterpene found in the provinces of Loja and Zamora-Chinchipe. In this study, we showed that DhL displayed cytostatic and cytotoxic activities on the human cerebral astrocytoma D384 cell line. With lactone isolated from Gynoxys verrucosa Wedd, a medicinal plant from Ecuador, we found that DhL induced cell death in D384 cells by triggering cell cycle arrest and inducing apoptosis and DNA damage. We further found that the cell death resulted in the increased expression of CDKN1A and BAX proteins. A marked induction of the levels of total TP73 and phosphorylated TP53, TP73, and γ-H2AX proteins was observed in D384 cells exposed to DhL, but no increase in total TP53 levels was detected. Overall these studies demonstrated the marked effect of DhL on the diminished survival of human astrocytoma cells through the induced expression of TP73 and phosphorylation of TP73 and TP53, suggesting their key roles in the tumor cell response to DhL treatment.
authors: Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México, D. F., Mexico; Departamento de Ciencias de la Salud, Universidad Técnica Particular de Loja, Loja, Ecuador.
authors: Natalia
authors: N
authors: Bailon-Moscoso
authors: Departamento de Ciencias de la Salud, Universidad Técnica Particular de Loja, Loja, Ecuador.
authors: Gabriela
authors: G
authors: González-Arévalo
authors: Departamento de Ciencias de la Salud, Universidad Técnica Particular de Loja, Loja, Ecuador.
authors: Gabriela
authors: G
authors: Velásquez-Rojas
authors: Departamento de Química Aplicada, Universidad Técnica Particular de Loja, Loja, Ecuador; Dipartimento di Chimica Organica, University of Pavia, Pavia, Italy.
authors: Omar
authors: O
authors: Malagon
authors: Dipartimento di Chimica Organica, University of Pavia, Pavia, Italy.
authors: Giovanni
authors: G
authors: Vidari
authors: Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México, D. F., Mexico; Departamento de Bioquímica, Instituto Nacional de Ciencias Médicas y Nutrición"Salvador Zubirán", México, D. F., Mexico.
authors: Alejandro
authors: A
authors: Zentella-Dehesa
authors: Departamento de Ciencias de la Salud, Universidad Técnica Particular de Loja, Loja, Ecuador; Head and Neck Cancer Research Division, Johns Hopkins University School of Medicine, Baltimore, United States of America.
authors: Edward A
authors: EA
authors: Ratovitski
authors: Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México, D. F., Mexico.
authors: Patricia
authors: P
authors: Ostrosky-Wegman
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001254:Astrocytoma / Q000188:drug therapy*; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis; D004249:DNA Damage / Q000187:drug effects*; D004268:DNA-Binding Proteins / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D007783:Lactones / Q000494:pharmacology*; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D064210:Secondary Metabolism; D012717:Sesquiterpenes / Q000494:pharmacology*; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C494826:BAX protein, human; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins; C468783:H2AX protein, human; D006657:Histones; D007783:Lactones; D009687:Nuclear Proteins; D012717:Sesquiterpenes; C495901:TP53 protein, human; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D051028:bcl-2-Associated X Protein; C079949:dehydroleucodine