RESUMEN

Polyphyllin VII is a biologically active herbal monomer extracted from the traditional Chinese herbal medicine Chonglou. Many studies have demonstrated the anticancer activity of polyphyllin VII against various types of cancers, such as colon, liver, and lung cancer, but its effect on breast cancer has not been elucidated. In this study, we demonstrate that polyphyllin VII inhibited proliferation, increased production of intracellular reactive oxygen species, and decreased mitochondrial membrane potential in breast cancer cells. Notably, polyphyllin VII also induced apoptosis via the mitochondrial pathway. Transcriptome sequencing was used to analyze the targets of PPVII in regulating breast cancer cells. Mechanistic studies showed that polyphyllin VII downregulated Son of Sevenless1 (SOS1) and inhibited the MAPK/ERK pathway. Furthermore, PPVII exerted strong antitumor effects in vivo in nude mice injected with breast cancer cells. Our results suggest that PPVII may promote apoptosis through regulating the SOS1/MAPK/ERK pathway, making it a possible candidate target for the treatment of breast cancer.

Asunto(s)

Apoptosis , Neoplasias de la Mama , Regulación hacia Abajo , Sistema de Señalización de MAP Quinasas , Proteína SOS1 , Apoptosis/efectos de los fármacos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Neoplasias de la Mama/genética , Animales , Humanos , Femenino , Regulación hacia Abajo/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Proteína SOS1/metabolismo , Proteína SOS1/genética , Ratones Desnudos , Saponinas/farmacología , Saponinas/uso terapéutico , Proliferación Celular/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Ratones , Línea Celular Tumoral , Medicamentos Herbarios Chinos/farmacología , Fitoterapia , Antineoplásicos Fitogénicos/farmacología , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratones Endogámicos BALB C