Raddeanin A exerts potent efficacy against non-small cell lung cancer by inhibiting cyclin-dependent kinase 6

IF 5 2区医学 Q2 Medicine

Translational Oncology Pub Date : 2025-04-11 DOI:10.1016/j.tranon.2025.102382

Xian Wang , Xiao Lin , Yuxin Liu , Chunbo Ma , Mengchu Liu , Jiayu Bai , Yihan Ye , Chengguang Zhao , Lehe Yang , Xiaoying Huang , Liangxing Wang

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引用次数: 0

Abstract

Purpose

The aim of this study was to investigate the anti-tumor effects and mechanisms of Raddeanin A in NSCLC in vitro and in vivo.

Methods

The effects of Raddeanin A on cell cycle progression, proliferation, migration and invasion of NSCLC were assessed by flow cytometry and cell biological assays in multiple NSCLC cell lines. To identify possible targets of Raddeanin A in NSCLC, we employed a multifaceted approach incorporating network pharmacology, molecular docking, and molecular dynamics simulation, along with additional techniques such as SPR (Surface Plasmon Resonance), Co-IP (Co-Immunoprecipitation), and immunofluorescence. In vivo effects were investigated using a nude mouse xenograft tumor model.

Results

Raddeanin A inhibits NSCLC cell survival, inhibits invasion and migration and causes cell cycle arrest in G1 phase. Raddeanin A impacts NSCLC cellular activity by inhibiting CDK6, leading to anti-tumor effects. Molecular analysis confirms that the tight binding between Raddeanin A and CDK6, facilitated by specific hydrogen bonds at binding sites including VAL-101, HIS-100, GLN-149, LYS-147, THR-182, VAL-180, and ALA-23, stabilizes within the 40–100 ns interval. In a nude mouse xenograft tumor model, Raddeanin A also demonstrated an inhibitory effect on NSCLC tumor growth.

Conclusions

Raddeanin A blocks the cell cycle in G1 phase by inhibiting CDK6. Raddeanin A is expected to be a novel antitumor agent against NSCLC.

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来源期刊

Translational Oncology ONCOLOGY-

CiteScore

8.40

自引率

2.00%

发文量

314

审稿时长

54 days

期刊介绍： Translational Oncology publishes the results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of oncology patients. Translational Oncology will publish laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer. Peer reviewed manuscript types include Original Reports, Reviews and Editorials.