Xanthoxyletin blocks the RANK/RANKL signaling pathway to suppress the growth of human pancreatic cancer cells.

IF 2.1 4区医学 Q3 PHARMACOLOGY & PHARMACY

Acta Pharmaceutica Pub Date : 2023-09-14 Print Date: 2023-09-01 DOI:10.2478/acph-2023-0024

Xin Zhang, Luming Li, Yan Wu

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引用次数: 0

Abstract

Xanthoxyletin is a vital plant-derived bioactive coumarin. It has been shown to exhibit anticancer effects against different human cancers. Nonetheless, the anticancer effects of xanthoxyletin against human pancreatic cancer cells have not been evaluated. Against this backdrop, the present study was designed to evaluate the anticancer effects of xanthoxyletin in human pancreatic cancer cells and to decipher the underlying molecular mechanisms. The results revealed a significant (p < 0.05) upregulation of receptor activator of NF-kappaB (RANK), receptor activator of NF-kappaB ligand (RANKL) and osteoprotegerin (OPG) in human pancreatic tissues and cell lines at both transcriptional and translational levels. The administration of pancreatic cancer cells with xanthoxyletin diminished the viability of Capan-2 cells in a concentration-dependent manner and led to a significant decline in RANK, RANKL, and OPG expression. Silencing of RANK and xanthoxyletin treatment declined the viability of Capan-2 pancreatic cancer cells via induction of apoptosis. However, pancreatic cancer cells overexpressing RANK could rescue the growth inhibitory effects. Collectively, xanthoxyletin targets the RANK/RANKL signaling pathway in pancreatic cancer cells to induce cell apoptosis and may prove to be an important lead molecule.

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黄酮素能阻断 RANK/RANKL 信号通路，从而抑制人类胰腺癌细胞的生长。

黄腐素是一种重要的植物源生物活性香豆素。它已被证明对不同的人类癌症具有抗癌作用。然而，黄藤素对人类胰腺癌细胞的抗癌作用尚未得到评估。在此背景下，本研究旨在评估黄藤素对人类胰腺癌细胞的抗癌作用，并破译其潜在的分子机制。结果显示，在人胰腺组织和细胞系中，NF-kappaB受体激活因子（RANK）、NF-kappaB受体激活因子配体（RANKL）和骨保护素（OPG）在转录和翻译水平上都有明显的上调（p < 0.05）。给胰腺癌细胞施用黄腐素，会以浓度依赖的方式降低Capan-2细胞的活力，并导致RANK、RANKL和OPG的表达显著下降。通过诱导细胞凋亡，RANK 沉默和黄腐酸处理降低了 Capan-2 胰腺癌细胞的存活率。然而，过表达 RANK 的胰腺癌细胞可以挽救生长抑制作用。总之，黄腐素可靶向胰腺癌细胞的 RANK/RANKL 信号通路诱导细胞凋亡，可能被证明是一种重要的先导分子。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Acta Pharmaceutica PHARMACOLOGY & PHARMACY-

CiteScore

5.20

自引率

3.60%

发文量

审稿时长

>12 weeks

期刊介绍： AP is an international, multidisciplinary journal devoted to pharmaceutical and allied sciences and contains articles predominantly on core biomedical and health subjects. The aim of AP is to increase the impact of pharmaceutical research in academia, industry and laboratories. With strong emphasis on quality and originality, AP publishes reports from the discovery of a drug up to clinical practice. Topics covered are: analytics, biochemistry, biopharmaceutics, biotechnology, cell biology, cell cultures, clinical pharmacy, drug design, drug delivery, drug disposition, drug stability, gene technology, medicine (including diagnostics and therapy), medicinal chemistry, metabolism, molecular modeling, pharmacology (clinical and animal), peptide and protein chemistry, pharmacognosy, pharmacoepidemiology, pharmacoeconomics, pharmacodynamics and pharmacokinetics, protein design, radiopharmaceuticals, and toxicology.