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Casiopeina III-ia induces apoptosis in HCT-15 cells in vitro through caspase-dependent mechanisms and has antitumor effect in vivo

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Abstract

The aim of this study was to evaluate the in vitro and in vivo effects of the new chemotherapy agent Casiopeina III-ia [(4,4′-dimethyl-2,2′-bipiridine)(acetylacetonate) Copper (II) nitrate] on HCT-15 (p53–/-) colon cellular line. In vitro, the drug reduced the viability and induced necrosis and apoptosis in a dose dependent manner, without affecting cell cycle phases. Apoptosis was related to Bax increasing levels, suggesting a caspase-dependent mechanism of death, as verified by nucleosomal fragmentation of DNA. In vivo, the antitumor activity of Casiopeina III-ia was tested in HCT-15 cells transplanted to nude mice. In this study we will show that the novel antineoplastic agent Casiopeina III-ia is active on this colon tumor line, setting out as a good candidate for the treatment of colon tumors refractory to chemotherapy.

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Acknowledgments

This Project was realized with grants of CONACYT-2002-SALUD-C01-7677 and CONACYT U-41997MA1 sectorial projects. We thank Maria Elena Bravo for the synthesis and characterization of Cas III-ia. We also thank Emma Serrano for the preparation of the photographic material.

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Authors and Affiliations

  1. Department of Pathology, Faculty of Veterinary Medicine and Husbandry, Universidad Nacional Autónoma de México, Circuito interior 3000, Delegacion Coyoacan, Mexico, DF, 04510, Mexico

    Francisco Carvallo-Chaigneau, Carlos Cedillo-Peláez & Fernando Constantino-Casas

  2. Department of Neuroimmunology, Instituto de Neurología y Neurocirugía, SSA, Mexico, DF, 14269, Mexico

    Cristina Trejo-Solís

  3. Animal Experimentation Unit, Chemistry Faculty, Universidad Nacional Autónoma de México, Mexico, DF, 04510, Mexico

    Celedonio Gómez-Ruiz, Lucía Macías-Rosales & Isabel Gracia-Mora

  4. Department of Health and Biological Sciences, Universidad Autónoma Metropolitana-Iztapalapa, Mexico, DF, 09340, Mexico

    Ernesto Rodríguez-Aguilera & Edith Cortés-Barberena

  5. Department of Nuclear and Inorganic Chemistry, Chemistry Faculty, Universidad Nacional Autónoma de México, Mexico, DF, 04510, Mexico

    Isabel Gracia-Mora & Lena Ruiz-Azuara

  6. Center of Infectious Diseases Research, Instituto Nacional de Salud Pública, Cuernavaca, Morelos, 62508, Mexico

    Vicente Madrid-Marina

Authors
  1. Francisco Carvallo-Chaigneau
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  2. Cristina Trejo-Solís
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  3. Celedonio Gómez-Ruiz
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  4. Ernesto Rodríguez-Aguilera
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  5. Lucía Macías-Rosales
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  6. Edith Cortés-Barberena
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  7. Carlos Cedillo-Peláez
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  8. Isabel Gracia-Mora
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  9. Lena Ruiz-Azuara
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  10. Vicente Madrid-Marina
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  11. Fernando Constantino-Casas
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Corresponding author

Correspondence to Francisco Carvallo-Chaigneau.

Additional information

Lena Ruiz-Azuara - Previously as Lena Ruiz-Ramirez.

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Carvallo-Chaigneau, F., Trejo-Solís, C., Gómez-Ruiz, C. et al. Casiopeina III-ia induces apoptosis in HCT-15 cells in vitro through caspase-dependent mechanisms and has antitumor effect in vivo. Biometals 21, 17–28 (2008). https://doi.org/10.1007/s10534-007-9089-4

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