Caudatin potentiates the anti-tumor effects of TRAIL against human breast cancer by upregulating DR5.
Authors of this article are:
Fei HR, Yuan C, Wang GL, Zhao Y, Li ZJ, Du X, Wang FZ.
A summary of the article is shown below:
BACKGROUND: The ability of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) to preferentially induce apoptosis in transformed cells while sparing most normal cells is well established. However, the intrinsic and acquired resistance of tumors to TRAIL-induced apoptosis limits its therapeutic applicability.PURPOSE: We investigated the effect of caudatin, a species of C-21 steroidal glycosides isolated from the roots of Cynanchum auriculatum, on TRAIL-induced apoptosis in human breast cancer cells.METHODS: Cell growth inhibition was evaluated by the CCK-8 assay. The cell cycle distribution was assessed by propidium iodide flow cytometry. Apoptosis was determined by TUNEL staining. Protein expression was detected by western blotting analysis.RESULTS: Caudatin enhanced TRAIL-induced apoptosis in human breast cancer cells. This sensitization was achieved by upregulating death receptor 5 (DR5). Knockdown of DR5 abolished the enhancing effect of caudatin on TRAIL responses. The caudatin-induced upregulation of DR5 was accompanied by increased expression of CHOP and phosphorylation of p38 MAPK and JNK. CHOP knockdown blocked caudatin-upregulated DR5 expression. Moreover, cotreatment of breast cancer cells with p38 MAPK and JNK inhibitors significantly counteracted the caudatin-induced expression of DR5.CONCLUSION: Our results showed that caudatin sensitized breast cancer cells to TRAIL-induced apoptosis through activation of CHOP, p38 MAPK and JNK-mediated upregulation of DR5 expression. The combination of TRAIL and caudatin may be a promising therapeutic approach for the treatment of breast cancer.Copyright © 2019 Elsevier GmbH. All rights reserved.
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This article is a good source of information and a good way to become familiar with topics such as: CHOP; Caudatin; DR5; MAPK; TRAIL.
