title: Apoptotic and autophagic cell death induced by glucolaxogenin in cervical cancer cells.
abstract: The antiproliferative and cytotoxic activity of glucolaxogenin and its ability to induce apoptosis and autophagy in cervical cancer cells are reported. We ascertained that glucolaxogenin exerts an inhibitory effect on the proliferation of HeLa, CaSki and ViBo cells in a dose-dependent manner. Analysis of DNA distribution in the cell-cycle phase of tumor cells treated with glucolaxogenin suggests that the anti-proliferative activity of this steroid is not always dependent on the cell cycle. Cytotoxic activity was evaluated by detection of the lactate dehydrogenase enzyme in supernatants from tumor cell cultures treated with the steroid. Glucolaxogenin exhibited null cytotoxic activity. With respect to the apoptotic activity, the generation of apoptotic bodies, the presence of active caspase-3 and annexin-V, as well as the DNA fragmentation observed in all tumor lines after treatment with glucolaxogenin suggests that this compound does indeed induce cell death by apoptosis. Also, a significantly increased presence of the LC3-II, LC3 and Lamp-1 proteins was evidenced with the ultrastructural existence of autophagic vacuoles in cells treated with this steroidal glycoside, indicating that glucolaxogenin also induces autophagic cell death. It is important to note that this compound showed no cytotoxic effect and did not affect the proliferative capacity of mononuclear cells obtained from normal human peripheral blood activated by phytohaemagglutinin. Thus, glucolaxogenin is a compound with anti-proliferative properties that induces programmed cell death in cancer cell lines, though it is selective with respect to normal lymphocytic cells. These findings indicate that this glycoside could have a selective action on tumor cells and, therefore, be worthy of consideration as a therapeutic candidate with anti-tumor potential.
authors.affiliation: Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónoma de México, 09230, Mexico, DF, Mexico. luisss@unam.mx.|Centro de Investigación UNAM-UABJO, Oaxaca, Mexico. luisss@unam.mx.
authors.forename: L
authors.initials: L
authors.lastname: Sánchez-Sánchez
authors.affiliation: Lab. de Microscopía Electrónica. Departamento de Biología Celular, Facultad de Ciencias, Universidad Nacionsal Autónoma de México, Ciudad Universitaria, 04510, Mexico, DF, Mexico.
authors.forename: M L
authors.initials: ML
authors.lastname: Escobar
authors.affiliation: Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Ciudad Universitaria, 72570, Puebla, Pue, Mexico. jesus.sandoval@correo.buap.mx.
authors.forename: J
authors.initials: J
authors.lastname: Sandoval-Ramírez
authors.affiliation: Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónoma de México, 09230, Mexico, DF, Mexico.
authors.forename: H
authors.initials: H
authors.lastname: López-Muñoz
authors.affiliation: Departamento de Física Aplicada, Centro de Investigación y de Estudios Avanzados, Unidad Mérida, Km. 6 Antigua Carretera a Progreso Apdo. Postal 73, Cordemex, 97310, Mérida, Yuc, Mexico. mfernandez@mda.cinvestav.mx.
authors.forename: M A
authors.initials: MA
authors.lastname: Fernández-Herrera
authors.affiliation: Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónoma de México, 09230, Mexico, DF, Mexico.
authors.forename: J M V
authors.initials: JM
authors.lastname: Hernández-Vázquez
authors.affiliation: Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Ciudad Universitaria, 72570, Puebla, Pue, Mexico.
authors.forename: C
authors.initials: C
authors.lastname: Hilario-Martínez
authors.affiliation: Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad Universitaria, 04510, Mexico, DF, Mexico.|Centro de Investigación UNAM-UABJO, Oaxaca, Mexico.
authors.forename: E
authors.initials: E
authors.lastname: Zenteno
mesh_terms: D017304:Annexin A5 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D005260:Female; D006027:Glycosides / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D010835:Phytohemagglutinins / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D017304:Annexin A5; D000970:Antineoplastic Agents; D006027:Glycosides; D010835:Phytohemagglutinins; D007770:L-Lactate Dehydrogenase; D053148:Caspase 3
keywords: Apoptosis; Autophagy; Cancer; Glucolaxogenin