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Caudatin Potentiates the Anti-Tumor Effects of TRAIL Against Human Breast Cancer by Upregulating DR5

Caudatin Potentiates the Anti-Tumor Effects of TRAIL Against Human Breast Cancer by Upregulating DR5

Hong-Rong Fei, Chuang Yuan, Gui-Ling Wang, Ying Zhao, Zhao-Jun Li, Xin Du, Feng-Ze Wang

Phytomedicine. 2019 Sep;62:152950.

PMID: 31102888

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP38395027	Caudatin		38395-02-7	Price
IAR42412950	TRAIL human			Price

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