Traditional herbal medicine-derived sulforaphene promotes mitophagic cell death in lymphoma cells through CRM1-mediated p62/SQSTM1 accumulation and AMPK activation.
Chem Biol Interact
; 281: 11-23, 2018 Feb 01.
Article
en En
| MEDLINE
| ID: mdl-29247643
ABSTRACT
Sulforaphene (LFS-01) is the major chemical constituent of Raphanus sativus, a medicinal herb used for over a thousand years in traditional Chinese medicine. Here we identified that LFS-01 can selectively eradicate lymphoma cells while sparing normal lymphocytes by triggering concomitant mitophagy and apoptosis. We demonstrated that LFS-01 can retain Nrf2 in the nucleus by covalently modulating CRM1 and consequently upregulate p62/SQSTM1, an essential structural component of the autophagosomes during mitophagic process. We found that LFS-01 treatment also stimulated AMPK and thereby inhibited the mTOR pathway. On the contrary, we revealed that AMPK inhibition can severely impair the LFS-01-mediated mitophagy. Transcriptomic studies confirmed that 15 autophagy-associated genes such as p62/SQSTM1, VCP and BCL2 were differentially expressed after LFS-01 treatment. Furthermore, protein interactome network analysis revealed that the events of apoptosis and the assembly of autophagy vacuole were significant upon LFS-01 exposure. Lastly, we found that LFS-01 exhibited strong efficacy in xenograft mouse model yet with the lack of apparent toxicity to animals. We concluded that LFS-01 triggered mitophagic cell death via CRM1-mediated p62 overexpression and AMPK activation. Our findings provide new insights into the mechanism of action for LFS-01 and highlight its potential applications in treating major human diseases.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Medicinas Tradicionales:
Medicinas_tradicionales_de_asia
/
Medicina_china
/
Medicina_japonesa
Asunto principal:
Medicamentos Herbarios Chinos
/
Apoptosis
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Receptores Citoplasmáticos y Nucleares
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Isotiocianatos
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Carioferinas
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Proteínas Quinasas Activadas por AMP
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Mitofagia
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Proteína Sequestosoma-1
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Chem Biol Interact
Año:
2018
Tipo del documento:
Article
País de afiliación:
China