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

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

doi:10.1016/j.tranon.2025.102382

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

Transl Oncol. 2025 Jun:56:102382. doi: 10.1016/j.tranon.2025.102382. Epub 2025 Apr 11.

Authors

Xian Wang¹, Xiao Lin², Yuxin Liu², Chunbo Ma², Mengchu Liu², Jiayu Bai², Yihan Ye², Chengguang Zhao³, Lehe Yang⁴, Xiaoying Huang⁵, Liangxing Wang⁶

Affiliations

¹ Pulmonary Division, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou Key Laboratory of Interdiscipline and Translational Medicine, Wenzhou Key Laboratory of Heart and Lung, Wenzhou, Zhejiang 325035, China; School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China; Shanghai Fengxian District Central Hospital, No. 6600, Nanfeng Highway, Fengxian District, Shanghai 201499, China.
² Pulmonary Division, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou Key Laboratory of Interdiscipline and Translational Medicine, Wenzhou Key Laboratory of Heart and Lung, Wenzhou, Zhejiang 325035, China.
³ School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
⁴ Pulmonary Division, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou Key Laboratory of Interdiscipline and Translational Medicine, Wenzhou Key Laboratory of Heart and Lung, Wenzhou, Zhejiang 325035, China. Electronic address: yanglehe@wmu.edu.cn.
⁵ Pulmonary Division, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou Key Laboratory of Interdiscipline and Translational Medicine, Wenzhou Key Laboratory of Heart and Lung, Wenzhou, Zhejiang 325035, China. Electronic address: huangxiaoying@wmu.edu.cn.
⁶ Pulmonary Division, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou Key Laboratory of Interdiscipline and Translational Medicine, Wenzhou Key Laboratory of Heart and Lung, Wenzhou, Zhejiang 325035, China. Electronic address: wangliangxing@wzhospital.cn.

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.

Keywords: CDK6; Cycle arrest; NSCLC; Raddeanin A; inhibitor.