Tanshinone-1 induces tumor cell killing, enhanced by inhibition of secondary activation of signaling networks.
Cell Death Dis
; 4: e905, 2013 Nov 07.
Article
en En
| MEDLINE
| ID: mdl-24201804
Tumor multidrug resistance (MDR) can result from overexpression of drug transporters and deregulation of cellular signaling transduction. New agents and strategies are required for overcoming MDR. Here, we report that tanshinone-1, a bioactive ingredient in traditional Chinese medicine, directly killed MDR tumor cells and their corresponding parental cells, which was potentiated by inhibition of secondary activation of signaling networks. Tanshinone-1 was slightly more potent at inducing cytotoxicity and apoptosis in MDR cells than in corresponding parental cells. Tanshinone-1-induced MDR cell killing was independent of the function and expression of drug transporters but was partially correlated with the phosphatase-dependent reduction of phospho-705-Stat3, which secondarily activated p38-, AKT-, and ERK-involved signaling networks. Cotreatments with p38, AKT, and ERK inhibitors potentiated the anti-MDR effects of tanshinone-1. Our study presents a model for MDR cell killing using a compound of natural origin. This model could lead to new therapeutic strategies for targeting signaling network(s) in MDR cancers as well as new strategies for multitarget design.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Abietanos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Death Dis
Año:
2013
Tipo del documento:
Article
Pais de publicación:
Reino Unido