期刊
MOLECULES
卷 24, 期 22, 页码 -出版社
MDPI
DOI: 10.3390/molecules24224100
关键词
TNF-alpha; dicentrine; apoptosis; metastasis; lung adenocarcinoma
资金
- Faculty of Medicine Research Found, Chiang Mai University [014-2560]
Numerous studies have indicated that tumor necrosis factor-alpha (TNF-alpha) could induce cancer cell survival and metastasis via activation of transcriptional activity of NF-kappa B and AP-1. Therefore, the inhibition of TNF-alpha -induced NF-kappa B and AP-1 activity has been considered in the search for drugs that could effectively treat cancer. Dicentrine, an aporphinic alkaloid, exerts anti-inflammatory and anticancer activities. Therefore, we investigated the effects of dicentrine on TNF-alpha -induced tumor progression in A549 lung adenocarcinoma cells. Our results demonstrated that dicentrine effectively sensitizes TNF-alpha -induced apoptosis in A549 cells when compared with dicentrine alone. In addition, dicentrine increases caspase-8, -9, -3, and poly (ADP-ribose) polymerase (PARP) activities by upregulating the death-inducing signaling complex and by inhibiting the expression of antiapoptotic proteins including cIAP2, cFLIP, and Bcl-XL. Furthermore, dicentrine inhibits the TNF-alpha -induced A549 cells invasion and migration. This inhibition is correlated with the suppression of invasive proteins in the presence of dicentrine. Moreover, dicentrine significantly blockes TNF-alpha -activated TAK1, p38, JNK, and Akt, leading to reduced levels of the transcriptional activity of NF-kappa B and AP-1. Taken together, our results suggest that dicentrine could enhance TNF-alpha -induced A549 cell death by inducing apoptosis and reducing cell invasion due to, at least in part, the suppression of TAK-1, MAPK, Akt, AP-1, and NF-kappa B signaling pathways.
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