Antitumor Activity of Isalpinin from Paphiopedilum dianthum on Non-Small Cell Lung Cancer Cell Lines

Sep 24, 2026

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Lung cancer is a major cause of cancer-related death worldwide, and current therapies are constrained by drug resistance, metastasis, and tumor heterogeneity. This study evaluates the anticancer activity of isalpinin, a flavonoid isolated from Paphiopedilum dianthum, against NSCLC cell lines A549, H23, and H460. Isalpinin markedly reduces viability in a dose- and time-dependent manner, suppressing proliferation, migration, and anchorage-independent growth. Mechanistically, it triggers apoptosis through increased ROS production and Bcl-2 downregulation and directly binds AKT1 in docking studies.

LanguageEnglish

CategoryHealthcare

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Pages27

Reading Time1 h 8 min

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Abstract

Introduction

Article Antitumor Activity of Isalpinin from Paphiopedilum dianthumon Non-Small Cell Lung Cancer Cell Lines Phisit Pouyfung 1,2, Nonthalert Lertnitikul 3,4, Hua Bai 5, Achitphol Chookaew 6, Varisa Pongrakhananon 7,8, Piriya Chonsut 9 and Suwichak Chaisit 2,10, * Academic Editors: Mª Ángeles Castro and William Setzer Received: 12 May 2025 Revised: 23 June 2025 Accepted: 24 June 2025 Published: 27 June 2025 Citation: Pouyfung, P.; Lertnitikul, N.; Bai, H.; Chookaew, A.; Pongrakhananon, V.; Chonsut, P.; Chaisit, S. Antitumor Activity of Isalpinin from Paphiopedilum dianthumon Non-Small Cell Lung Cancer Cell Lines. Molecules 2025, 30, 2762 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)molecules30132762 Copyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://creativecommons.org/](https://creativecommons.org/)[ ](https://creativecommons.org/)[licenses/by/4.0/](licenses/by/4.0/)) . 1 Department of Occupational Health and Safety, School of Public Health, Walailak University, Nakhon Si Thammarat 80160, Thailand; [phisit.po@mail.wu.ac.th](phisit.po@mail.wu.ac.th) 2 Biomass and Oil Palm Center of Excellence, Walailak University, Nakhon Si Thammarat 80160, Thailand 3 Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand; [nonthalert.l@chula.ac.th](nonthalert.l@chula.ac.th) 4 Animal Models of Chronic Inflammation-Associated Diseases for Drug Discovery Research Unit, Chulalongkorn University, Bangkok 10330, Thailand 5 College of Public Health, Kunming Medical University, Kunming 650500, China; [baihua@kmmu.edu.cn](baihua@kmmu.edu.cn) 6 Division of Hematopoiesis, Joint Research Center for Human Retrovirus Infection and Graduate School of Medical Sciences, Kumamoto University, Honjo, Chuou-ku, Kumamoto 860-0811, Japan; [achitphol.ch@gmail.com](achitphol.ch@gmail.com) 7 Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand; [varisa.p@pharm.chula.ac.th](varisa.p@pharm.chula.ac.th) 8 Center of Excellence in Preclinical Toxicity and Efficacy Assessment of Medicines and Chemicals, Chulalongkorn University, Bangkok 10330, Thailand 9 Department of Applied Thai Traditional Medicine, School of Medicine, Walailak University, Nakhon Si Tammarat 80160, Thailand; [piriya.ch@wu.ac.th](piriya.ch@wu.ac.th) 10 Department of Chemical Engineering and Pharmaceutical Chemistry, School of Engineering and Technology, Walailak University, Nakhon Si Thammarat 80160, Thailand * Correspondence: [suwichak.ch@mail.wu.ac.th](suwichak.ch@mail.wu.ac.th); Tel.: +66-0-7567-6769 Abstract Lung cancer is a leading cause of cancer-related deaths globally, with current treatments having significant limitations, including drug resistance, metastasis, and tumor heterogeneity. This study investigated the anticancer potential of isalpinin, a flavonoid isolated from Paphiopedilum dianthum, against non-small cell lung cancer (NSCLC) cell lines A549, H23, and H460 . Isalpinin significantly inhibited NSCLC cell viability in a dose-and timedependent manner; H23 and H460 cells showed greater sensitivity (IC 50 a ~ 44 µM at 48 h) compared to A549 cells (IC 50 82 µM) . Isalpinin suppressed proliferation, migration, and anchorage-independent growth, particularly in H23/H460 cells. Mechanistically, it induced apoptosis via increased ROS production and Bcl-2 downregulation, particularly in H23 and H460 cells. In a molecular docking analysis, isalpinin was found to directly bind to the ATP-binding pocket of AKT1, as confirmed by reduced Akt/GSK3β phosphorylation. These results suggest that isalpinin showed a potent multi-target natural compound against NSCLC that disrupts the key hallmarks of malignanc

FAQs

What compound is investigated, and where is it isolated from?

The study investigates isalpinin, a flavonoid isolated from Paphiopedilum dianthum.

Which NSCLC cell lines are used to test anticancer effects?

Anticancer activity is evaluated in NSCLC cell lines A549, H23, and H460.

How does isalpinin induce anticancer mechanisms in NSCLC cells?

Isalpinin suppresses viability and key cancer behaviors and induces apoptosis associated with increased ROS production and Bcl-2 downregulation, with docking suggesting direct binding to AKT1.

Sep 24, 2026

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