ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Pharmacology of Anti-Cancer Drugs
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1555802
This article is part of the Research TopicEnhancing Cancer Therapy: Integrating Plant-Derived Bioactives with Chemotherapy through Traditional Knowledge and Modern AdvancesView all 10 articles
Isoliensinine exerts antitumor effects in Lung adenocarcinoma by inhibiting APEX1-driven ROS production
Provisionally accepted
- 1Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of Soochow University, Suzhou, Suzhou, Liaoning Province, China
- 2Department of Anesthesiology, Zhejiang Cancer Hospital, Hangzhou, China
- 3Department of Pharmacy, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China
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Lung cancer is considered to be the world's leading malignancy in morbidity and mortality, and despite great efforts to treat it no effective treatment has yet been found.Isoliensinine is a natural small-molecule drug with potent anti-tumor activity in several cancer cell lines. Here, we have shown that Isoliensinine exhibits anti-tumor activity against lung adenocarcinoma (LUAD) both in vitro and in vivo.The biological functions of Isoliensinine in LUAD cells were investigated using CCK8 assay, colony formation, transwell assays and flow cytometry assays. DARTS assay was used to validate Isoliensinine targets screened by site prediction and molecular docking. The in vivo anti-tumor efficacy of Isoliensinine was analyzed in the xenograft tumor model.The IC50 of Isoliensinine were 6.98 μM, 17.24 μM and 16.00 μM in H1299, A549, H1650 cell lines while 28.65 μM in BEAS-2B cells. Isoliensinine inhibits the proliferation, migration, invasion of LUAD cells and arrests the cell cycle and promotes LUAD cells apoptosis in vitro. Isoliensinine attenuates tumor growth in a murine xenograft mode. Mechanistically, Isoliensinine interacted directly with APEX1, inhibited APEX1 protein levels, and promoted ROS generation. Knockdown of APEX1 reverses the effect of Isoliensinine on LUAD cells.Isoliensinine exerts antitumor effects through inhibition of APEX1 driven ROS production, therefore, Isoliensinine may represent a new drug candidate to be used to treat LUAD.
Keywords: Isoliensinine, Lung Adenocarcinoma, APEX1, Reactive Oxygen Species, natural compound
Received: 05 Jan 2025; Accepted: 28 Apr 2025.
Copyright: © 2025 Chen, Shu, Shen, Yan, Liu and Huang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Zeyi Liu, Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of Soochow University, Suzhou, Suzhou, Liaoning Province, China
Jian-An Huang, Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of Soochow University, Suzhou, Suzhou, Liaoning Province, China
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