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Apoptotic and autophagic cell death induced by glucolaxogenin in cervical cancer cells

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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.

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Acknowledgments

This work was supported by CONACyT Grants 180526, 176858, and 176863. We thank PAPIIT IN222114, VIEP-BUAP, and CUVyTT-BUAP for academic and financial support. This paper constitutes a partial fulfilment of the Doctorado en Ciencias Médicas y Biológicas of the Universidad Autónoma Benito Juárez de Oaxaca, México. The work in Mérida is supported by the L’Oréal-UNESCO For Women in Science program, the Mexican Academy of Science and CONACyT. The authors would like to thank Paul C. Kersey Johnson for reviewing the English word usage and grammar.

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Authors and Affiliations

  1. Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónoma de México, 09230, Mexico, DF, Mexico

    L. Sánchez-Sánchez, H. López-Muñoz & J. M. V. Hernández-Vázquez

  2. Lab. de Microscopía Electrónica. Departamento de Biología Celular, Facultad de Ciencias, Universidad Nacionsal Autónoma de México, Ciudad Universitaria, 04510, Mexico, DF, Mexico

    M. L. Escobar

  3. Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Ciudad Universitaria, 72570, Puebla, Pue, Mexico

    J. Sandoval-Ramírez & C. Hilario-Martínez

  4. 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

    M. A. Fernández-Herrera

  5. Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad Universitaria, 04510, Mexico, DF, Mexico

    E. Zenteno

  6. Centro de Investigación UNAM-UABJO, Oaxaca, Mexico

    L. Sánchez-Sánchez & E. Zenteno

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  1. L. Sánchez-Sánchez
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Correspondence to L. Sánchez-Sánchez, J. Sandoval-Ramírez or M. A. Fernández-Herrera.

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Sánchez-Sánchez, L., Escobar, M.L., Sandoval-Ramírez, J. et al. Apoptotic and autophagic cell death induced by glucolaxogenin in cervical cancer cells. Apoptosis 20, 1623–1635 (2015). https://doi.org/10.1007/s10495-015-1181-6

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  • DOI: https://doi.org/10.1007/s10495-015-1181-6

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