A triple-drug combination induces apoptosis in cervical cancer-derived cell lines
Por:
Delgado-Waldo, Izamary, Contreras-Romero, Carlos, Salazar-Aguilar, Sandra, Pessoa, Joao, Mitre-Aguilar, Irma, Garcia-Castillo, Veronica, Perez-Plasencia, Carlos, Jacobo-Herrera, Nadia Judith
Publicada:
8 may 2023
Resumen:
IntroductionCervical cancer is a worldwide health problem due to the
number of deaths caused by this neoplasm. In particular, in 2020, 30,000
deaths of this type of tumor were reported in Latin America. Treatments
used to manage patients diagnosed in the early stages have excellent
results as measured by different clinical outcomes. Existing first-line
treatments are not enough to avoid cancer recurrence, progression, or
metastasis in locally advanced and advanced stages. Therefore, there is
a need to continue with the proposal of new therapies. Drug
repositioning is a strategy to explore known medicines as treatments for
other diseases. In this scenario, drugs used in other pathologies that
have antitumor activity, such as metformin and sodium oxamate, are
analyzed. MethodsIn this research, we combined the drugs metformin and
sodium oxamate with doxorubicin (named triple therapy or TT) based on
their mechanism of action and previous investigation of our group
against three CC cell lines. ResultsThrough flow cytometry, Western
blot, and protein microarray experiments, we found TT-induced apoptosis
on HeLa, CaSki, and SiHa through the caspase 3 intrinsic pathway,
including the critical proapoptotic proteins BAD, BAX, cytochrome-C, and
p21. In addition, mTOR and S6K phosphorylated proteins were inhibited in
the three cell lines. Also, we show an anti-migratory activity of the
TT, suggesting other targets of the drug combination in the late CC
stages. DiscussionThese results, together with our former studies,
conclude that TT inhibits the mTOR pathway leading to cell death by
apoptosis. Our work provides new evidence of TT against cervical cancer
as a promising antineoplastic therapy.
Filiaciones:
Delgado-Waldo, Izamary:
Unidad de Bioquímica Guillermo Soberón Acevedo, Instituto de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, Mexico
Posgrado en Ciencias Biológicas, Universidad Nacional Autónoma de México, Copilco Universidad, Coyoacán, Mexico
Inst Ciencias Med & Nutr Salvador Zubiran, Unidad Bioquim Guillermo Soberon Acevedo, Tlalpan, Mexico
Univ Nacl Autonoma Mexico, Posgrad Ciencias Biol, Coyoacan, Mexico
Contreras-Romero, Carlos:
Posgrado en Ciencias Biológicas, Universidad Nacional Autónoma de México, Copilco Universidad, Coyoacán, Mexico
Laboratorio de Genómica, Instituto Nacional de Cancerología, Tlalpan, Mexico
Univ Nacl Autonoma Mexico, Posgrad Ciencias Biol, Coyoacan, Mexico
Inst Nacl Cancerol, Lab Genom, Tlalpan, Mexico
Salazar-Aguilar, Sandra:
Laboratorio de Hematopoiesis y Leucemia, Unidad de Investigación, Diferenciación Celular y Cáncer, Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónoma de México, Iztapalapa, Mexico
Univ Nacl Autonoma Mexico, Fac Estudios Super Zaragoza, Unidad Invest, Lab Hematopoiesis & Leucemia, Iztapalapa, Mexico
Pessoa, Joao:
CNC - Center for Neuroscience and Cell Biology, CIBB - Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal
Univ Coimbra, CNC Ctr Neurosci & Cell Biol, CIBB Ctr Innovat Biomed & Biotechnol, Coimbra, Portugal
Mitre-Aguilar, Irma:
Unidad de Bioquímica Guillermo Soberón Acevedo, Instituto de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, Mexico
Inst Ciencias Med & Nutr Salvador Zubiran, Unidad Bioquim Guillermo Soberon Acevedo, Tlalpan, Mexico
Garcia-Castillo, Veronica:
Laboratorio de Genómica Funcional, Unidad de Biomedicina, FES-IZTACALA, Universidad Nacional Autónoma de México, Tlalnepantla, Mexico
Univ Nacl Autonoma Mexico, Unidad Biomed, Lab Genomica Func, FES IZTACALA, Tlalnepantla, Mexico
Perez-Plasencia, Carlos:
Laboratorio de Genómica, Instituto Nacional de Cancerología, Tlalpan, Mexico
Laboratorio de Genómica Funcional, Unidad de Biomedicina, FES-IZTACALA, Universidad Nacional Autónoma de México, Tlalnepantla, Mexico
Inst Nacl Cancerol, Lab Genom, Tlalpan, Mexico
Univ Nacl Autonoma Mexico, Unidad Biomed, Lab Genomica Func, FES IZTACALA, Tlalnepantla, Mexico
Jacobo-Herrera, Nadia Judith:
Unidad de Bioquímica Guillermo Soberón Acevedo, Instituto de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, Mexico
Inst Ciencias Med & Nutr Salvador Zubiran, Unidad Bioquim Guillermo Soberon Acevedo, Tlalpan, Mexico
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