Nelfinavir, an HIV protease inhibitor, induces apoptosis and cell cycle arrest in human cervical cancer cells via the ROS-dependent mitochondrial pathway.
Cancer Lett
; 364(1): 79-88, 2015 Aug 01.
Article
en En
| MEDLINE
| ID: mdl-25937300
ABSTRACT
HIV protease inhibitors (HIV-PIs) are a class of antiretroviral drugs designed to target the viral protease. Strikingly, these drugs have also been reported to possess antitumor effect. In this study, we evaluated the activity of one HIV-PI, Nelfinavir, against human cervical cancer cells. We found that Nelfinavir inhibited the growth of cervical cancer cell lines at the lowest micromolar concentrations clinically attainable. Nelfinavir promoted apoptosis and arrested the cell cycle at G1 phase. Apoptosis is attributed to the promotion of mitochondrial reactive oxygen species (ROS) production, which results in the translocation of mitochondrial apoptosis inducing factor (AIF) to the nucleus. We further showed that Nelfinavir increased mitochondrial ROS production by decreasing manganese superoxide dismutase (MnSOD) protein levels. Taken together, our results suggest that Nelfinavir can be repositioned as a cervical cancer therapeutic.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Ciclo Celular
/
Neoplasias del Cuello Uterino
/
Especies Reactivas de Oxígeno
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Inhibidores de la Proteasa del VIH
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Apoptosis
/
Nelfinavir
/
Potencial de la Membrana Mitocondrial
Límite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Cancer Lett
Año:
2015
Tipo del documento:
Article
País de afiliación:
China