Novel thiosemicarbazones induce high toxicity in estrogen-receptor-positive breast cancer cells (MCF7) and exacerbate cisplatin effectiveness in triple-negative breast (MDA-MB231) and lung adenocarcinoma (A549) cells

  • Estefany Ingrid Medina-Reyes
  • Marco Antonio Mancera-Rodríguez
  • Norma Laura Delgado-Buenrostro
  • Adriana Moreno-Rodríguez
  • Juan Luis Bautista-Martínez
  • Clara Estela Díaz-Velásquez
  • Stefanía Andrea Martínez-Alarcón
  • Hugo Torrens
  • María de los Ángeles Godínez-Rodríguez
  • Luis Ignacio Terrazas-Valdés
  • Yolanda Irasema Chirino
  • Felipe Vaca-PaniaguaEmail author


Cis-diamminedichloroplatinum(II) (CDDP), known as cisplatin, has been extensively used against breast cancer, which is the most frequent cancer among women, and lung cancer, the leading cancer that causes death worldwide. Novel compounds such as thiazole derivatives have exhibited antiproliferative activity, suggesting they could be useful against cancer treatment. Herein, we synthesized two novel thiosemicarbazones and an aldehyde to combine with CDDP to enhance efficacy against ER-positive breast MCF7 cancer cells, triple-negative/basal-B mammary carcinoma cells (MDA-MB231) and lung adenocarcinoma (A549) human cells. We synthesized 2,3,5,6-tetrafluoro-4-(2-mercaptoetanothiolyl)benzaldehyde (ALD), 5-[(2,3,5,6-tetrafluoro-4-(trifluoromethyl)phenyl)thio]-2-furaldehyde thiosemicarbazone (TSC1) and 5-[(4-(trifluoromethyl)phenyl)thio]-2-furaldehyde thiosemicarbazone (TSC2) and used them alone or in combination with subtoxic CDDP concentrations to evaluate cytotoxicity, cytoskeleton integrity and mitochondrial function. We found that none of the synthesized compounds improved CDDP activity against MCF7 cell cultures; however, TSC2 was effective in enhancing the cytotoxicity of CDDP against MDA-MB231 and A549 cancer cell cultures. We demonstrated that the cytotoxic effect is related to the TSC2 capacity to induce disruption in the cytoskeleton network and to decrease mitochondrial function.


Thiosemicarbazones Cytoskeleton disruption Mitochondrial dysfunction Breast cancer cells Lung cancer cells 



This research was supported by Programa de Apoyo a los Profesores de Carrera para Promover Grupos de Investigación (PAPCA, Facultad de Estudios Superiores Iztacala, UNAM; FESI-DIP-PAPCA-2014-36) and the National Council of Science and Technology (CONACyT 268769). Medina-Reyes Estefany Ingrid is a doctoral student from Programa de Doctorado en Ciencias Biomédicas de la Universidad Nacional Autónoma de México (UNAM) and received fellowship 576227 from CONACYT.

Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Supplementary material

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Estefany Ingrid Medina-Reyes
    • 1
  • Marco Antonio Mancera-Rodríguez
    • 1
  • Norma Laura Delgado-Buenrostro
    • 1
  • Adriana Moreno-Rodríguez
    • 2
  • Juan Luis Bautista-Martínez
    • 2
  • Clara Estela Díaz-Velásquez
    • 3
  • Stefanía Andrea Martínez-Alarcón
    • 1
  • Hugo Torrens
    • 4
  • María de los Ángeles Godínez-Rodríguez
    • 5
  • Luis Ignacio Terrazas-Valdés
    • 1
    • 3
  • Yolanda Irasema Chirino
    • 1
  • Felipe Vaca-Paniagua
    • 1
    • 3
    • 6
    Email author
  1. 1.Unidad de Biomedicina, Facultad de Estudios Superiores IztacalaUniversidad Nacional Autónoma de MéxicoTlalnepantlaMexico
  2. 2.Facultad de Ciencias QuímicasUniversidad Autónoma Benito JuárezOaxacaMexico
  3. 3.Laboratorio Nacional en Salud: Diagnóstico Molecular y Efecto Ambiental en Enfermedades Crónico-Degenerativas, Facultad de Estudios Superiores IztacalaUniversidad Nacional Autónoma de MéxicoTlalnepantlaMexico
  4. 4.Facultad de QuímicaUniversidad Nacional Autónoma de MéxicoCiudad de MéxicoMéxico
  5. 5.Carrera de Enfermería, Facultad de Estudios Superiores IztacalaUniversidad Nacional Autónoma de MéxicoTlalnepantlaMexico
  6. 6.Subdirección de Investigación BásicaInstituto Nacional de CancerologíaCiudad de MéxicoMexico

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