Posible nuevo mecanismo mitocondrial de la actividad anticancerígena de la vitamina C
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Lemeshko, V. V. (2022). Posible nuevo mecanismo mitocondrial de la actividad anticancerígena de la vitamina C. Rev. Acad. Colomb. Cienc. Ex. Fis. Nat., 46(178), 36–49. https://doi.org/10.18257/raccefyn.1575

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La característica principal de los tumores malignos de crecimiento rápido es el metabolismo de tipo Warburg, directamente relacionado con una cantidad extremadamente alta de hexoquinasa (HQ) unida a los canales aniónicos dependientes de voltaje (VDAC) en la membrana mitocondrial externa. En un estudio anterior se explicó el metabolismo de tipo Warburg como resultado de la supresión eléctrica de las mitocondrias debido al cierre de los VDAC libres, no unidos a HQ. En este se propone un posible nuevo mecanismo de la actividad anticancerígena de altas dosis de vitamina C (ascorbato) estimado mediante un modelo computacional simplificado. Según la hipótesis propuesta y el modelo, la oxidación de ascorbato en las mitocondrias conduce a la generación del potencial negativo de la membrana externa (PME), de signo opuesto al PME positivo generado por los complejos VDAC-HQ en las células cancerosas. El modelo demuestra que el PME negativo, incluso de magnitudes relativamente bajas, generado mediante cualquier mecanismo, lleva a la reapertura de los VDAC cerrados eléctricamente, reprogramando así el metabolismo energético celular. Según la hipótesis, los mediadores redox, que aumentan la tasa de oxidación de ascorbato en las mitocondrias, deberían aumentar sinérgicamente los efectos anticancerígenos de las dosis altas de ascorbato en concordancia con los datos experimentales reportados en la literatura. El modelo muestra que, incluso pequeños cambios en la sensibilidad al voltaje de los VDAC y/o de la cantidad de los complejos VDAC-HQ, causados por diversos factores fisiológicos como se sabe, podrían influir fuertemente en el mecanismo mitocondrial propuesto de la actividad anticancerígena del ascorbato.

https://doi.org/10.18257/raccefyn.1575

Palabras clave

Vitamina C | Actividad anticáncer | Metabolismo de Warburg | Mitocondrias | VDAC | Potencial de membrana externa mitocondrial
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Referencias

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