Lycorine targets multiple myeloma stem cell-like cells by inhibition of Wnt/ß-catenin pathway.
Br J Haematol
; 189(6): 1151-1164, 2020 06.
Article
em En
| MEDLINE
| ID: mdl-32167591
ABSTRACT
Multiple myeloma (MM) is characterised by the proliferation and accumulation of malignant plasma cells in the bone marrow. Despite the progress in treatment over the last few years, MM remains incurable and the majority of patients relapse. MM stem-like cells (MMSCs) have been considered as the main reason for drug resistance and eventual relapse. Currently, therapeutic agents are not enough to eradicate MMSCs, and finding effective strategies to eradicate MMSCs may improve the outcome of patients. Here we showed that lycorine, a natural compound from the Amaryllidaceae species, effectively inhibits the proliferation of myeloma cells from cell lines or patients, mainly through decreasing ALDH1+ cells. Mechanistically, lycorine decreases the MMSC population through inhibition of the Wnt/ß-catenin pathway by reducing the ß-catenin protein level. Moreover, lycorine could overcome the increasing proportion of ALDH1+ cells caused by bortezomib (BTZ) treatment, and a combination BTZ and lycorine have a synergistic effect on anti-myeloma cells. Furthermore, we found a similar reduction of MMSC characteristics by lycorine in BTZ-resistant MM cells and primary CD138+ plasma cells. Collectively, our findings indicate lycorine as a promising agent to target MMSCs to overcome the drug resistance of BTZ, and that, alone or in combination with BTZ, lycorine is a potential therapeutic strategy for MM treatments.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fenantridinas
/
Células-Tronco Neoplásicas
/
Alcaloides de Amaryllidaceae
/
Beta Catenina
/
Via de Sinalização Wnt
/
Mieloma Múltiplo
/
Proteínas de Neoplasias
Limite:
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article