Caudatin potentiates the anti-tumor effects of TRAIL against human breast cancer by upregulating DR5.

Autor: Fei HR; School of Pharmacy, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, 271016, PR China., Yuan C; School of Life Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, 271016, PR China., Wang GL; School of Pharmacy, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, 271016, PR China., Zhao Y; School of Life Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, 271016, PR China., Li ZJ; School of Pharmacy, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, 271016, PR China; School of Life Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, 271016, PR China., Du X; School of Life Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, 271016, PR China., Wang FZ; School of Life Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, 271016, PR China. Electronic address: fzwang@tsmc.edu.cn.
Jazyk: angličtina
Zdroj: Phytomedicine : international journal of phytotherapy and phytopharmacology [Phytomedicine] 2019 Sep; Vol. 62, pp. 152950. Date of Electronic Publication: 2019 May 06.
DOI: 10.1016/j.phymed.2019.152950
Abstrakt: 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.)
Databáze: MEDLINE
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