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El metabolismo del microbioma de los fitoquímicos alimentarios controla la actividad anticancerígena de los
Asael Roichman1, Qianying Zuo2, Sunghoon Hwang3
1Department of Chemistry, Princeton University, Princeton, NJ 08544, USA; Lewis-Sigler Institute of Integrative Genomics, Princeton University, Princeton, NJ, USA; Ludwig Institute for Cancer Research, Princeton Branch, Princeton, NJ, USA.
Cell
|May 20, 2025
Resumen
Los fitoquímicos de la dieta, no los macronutrientes, mejoran la terapia del cáncer con inhibidores de PI3K a través de las interacciones entre el microbioma y el hígado. Los microbios intestinales metabolizan los compuestos vegetales, afectando los niveles de fármacos y la eficacia contra el cáncer.
Área de la Ciencia:
- En el campo de la oncología
- Farmacología
- Microbiología
Sus antecedentes:
- La señalización de la fosfatidilinositol 3-cinasa (PI3K) es crucial en la respuesta a la insulina y con frecuencia está desregulada en el cáncer.
- Las dietas cetogénicas mejoran la eficacia del inhibidor PI3K en modelos de cáncer murino, potencialmente a través de la supresión de la insulina.
Objetivo del estudio:
- Investigar el mecanismo detrás de la sinergia entre la dieta y los inhibidores de PI3K en el tratamiento del cáncer.
- Determinar si la composición de macronutrientes de la dieta u otros factores median esta interacción.
Principales métodos:
- Comparación de la eficacia del inhibidor PI3K en modelos de cáncer murino alimentados con dietas diferentes (ketogénica frente a comida estándar).
- Análisis del contenido de fitoquímicos en las dietas y su metabolismo por el microbioma intestinal.
- Evaluación de la inducción hepática de la enzima citocromo P450 y los niveles de fármaco.
Principales resultados:
- La sinergia dieta-PI3K es independiente de la composición de los macronutrientes.
- Los fitoquímicos, específicamente las soyasaponinas, son metabolizados por el microbioma intestinal.
- El metabolismo del microbioma de los fitoquímicos induce las enzimas hepáticas, reduciendo los niveles sanguíneos de inhibidores de PI3K y su eficacia.
- Las dietas bajas en fitoquímicos y los antibióticos mejoran la actividad anticancerígena del inhibidor PI3K.
Conclusiones:
- El impacto de la dieta en la actividad de los fármacos contra el cáncer está mediado por las interacciones fitoquímicas- microbioma- hígado.
- El metabolismo del microbioma intestinal de los fitoquímicos de la dieta influye significativamente en la farmacocinética y la eficacia del inhibidor de PI3K.
- Las futuras terapias contra el cáncer pueden aprovechar la dieta y la modulación del microbioma para mejorar la actividad del fármaco.
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