Patchouli alcohol induces G0/G1 cell cycle arrest and apoptosis in vincristine-resistant non-small cell lung cancer through ROS-mediated DNA damage

Sep 24, 2026

Patchouli alcohol (PA) from Pogostemon cablin extract was investigated for anti-cancer activity against non-small cell lung cancer, focusing on vincristine-resistant A549/V16 cells. The study assessed PA-induced reactive oxygen species (ROS) production, ROS-mediated DNA damage, and downstream signaling via CHK1/CHK2. PA suppressed proliferation and colony formation, caused G0/G1 arrest via p53/p21 and CDK2/cyclin E1 regulation, and promoted apoptosis through the Bax/caspase-9/caspase-3 intrinsic pathway. PA also downregulated p-glycoprotein and stemness markers CD44/CD133 and showed synergistic inhibition with cisplatin.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages11

Reading Time28 min

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Abstract

Background

Methods

Results

Conclusions

Introduction

Lung cancer burden and treatment challenges

Vincristine and resistance in NSCLC

DOI: 10.1111/1759-7714.14982 ORIGINA L ARTICLE Patchouli alcohol induces G0/G 1 cell cycle arrest and apoptosis in vincristine-resistant non-small cell lung cancer through ROSmediated DNA damage Chi-Yen Liang 1 | Kai-Fu Chang 2 | Ya-Chih Huang 2,3 | Xiao-Fan Huang 2 | Gwo-Tarng Sheu 3 | Chia-Feng Kuo 2 | Chih-Yen Hsiao 4 | Nu-Man Tsai 2,5,6 1Division of Pulmonary Medicine, Department of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chia-Yi, Taiwan, ROC 2Department of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan, ROC 3Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan, ROC 4Division of Nephrology, Department of Internal Medicine, Ditmanson Medical Foundation ChiaYi Christian Hospital, Chia-Yi, Taiwan, ROC 5Clinical Laboratory, Chung Shan Medical University Hospital, Taichung, Taiwan, ROC 6Department of Life-and-Death Studies, Nanhua University, Chiayi, Taiwan, ROC Correspondence Chih-Yen Hsiao, Division of Nephrology, Department of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chia-Yi 60002, Taiwan, ROC. Email: [04504@cych.org.tw](04504@cych.org.tw) Nu-Man Tsai, Department of Medical Laboratory and Biotechnology, Chung Shan Medical University, No.110, Sec. 1, Jianguo N. Rd., Taichung City 40201, Taiwan, ROC. [Email:](Email: numan@csmu.edu.tw)[ numan@csmu.edu.tw](Email: numan@csmu.edu.tw) Funding information Ditmanson Medical Foundation Chia-Yi Christian Hospital, Grant/Award Number: R111-12; Ministry of Science and Technology, Taiwan, Grant/Award Numbers: MOST 109-2320-B- 040-012, MOST 110-2320-B-040-006, MOST 111-2320-B-040-022 Abstract Background: Lung cancer, especially non-small cell lung cancer (NSCLC), is one of the leading causes of cancer-related deaths worldwide. Vincristine (VCR) is a chemotherapeutic agent for lung cancers; however, its effectiveness is limited by side effects and the development of drug resistance. Patchouli alcohol (PA), from Pogostemon cablin extract, is known to possess anti-inflammatory and anticancer properties. In this study, we investigated the role of PA in inducing reactive oxygen species (ROS) -mediated DNA damage in A549 and VCR-resistant A549/V16 NSCLC cells. Methods: The anticancer potential of PA was studied using the MTT assay, colony formation, flow cytometry analysis, western blotting, DCFDA staining, immunofluorescence staining, and TUNEL assay techniques. Results: The intracellular ROS levels were enhanced in PA-treated cells, activating the CHK1 and CHK2 signaling pathways. PA further inhibited proliferation and colonyforming abilities and induced cell cycle arrest at the G0/G 1 phase by regulating p53/p21 and CDK2/cyclin E1 expression. Moreover, PA increased the percentage of cells in the subG 1 phase and induced apoptosis by activating the Bax/caspase-9/ caspase-3 intrinsic pathway. In addition, drug resistance (p-glycoprotein) and cancer stem cell (CD44 and CD133) markers were downregulated after PA treatment. Furthermore, combining PA and cisplatin exhibited synergistic inhibitory activity in A549 and A549/V16 cells. Conclusions: PA induced ROS-mediated DNA damage, triggered cell cycle arrest and apoptosis, attenuated drug resistance and cancer stem cell phenotypes, and synergistically inhibited proliferation in combination with cisplatin. These findings suggest that PA has the potential to be used for the treatment of NSCLC with or without VCR resistance. KEYW ORD S apoptosis, non-small cell lung cancer, patchouli alcohol, ROS, vincristine resistance INTRODUCTION Chi-Yen Liang and Kai-Fu Chang are two first authors contributed equally to this work. According to the Global Cancer Statistics 2020, from 185 countries for 36 cancers, lung cancer is the leading cause of cancer deaths worldwide, with approximately 2.2 million This is an open access article under the terms of the Creative Commons Attribution-

FAQs

How does patchouli alcohol affect vincristine-resistant NSCLC cells?

Patchouli alcohol increases intracellular ROS, leading to ROS-mediated DNA damage and triggering downstream CHK1/CHK2 signaling. It inhibits proliferation and induces both cell cycle arrest and apoptosis in A549 and VCR-resistant A549/V16 cells.

Which molecular pathways are involved in cell cycle arrest and apoptosis?

Cell cycle arrest at G0/G1 is regulated through p53/p21 and CDK2/cyclin E1 expression changes. Apoptosis is induced via the Bax/caspase-9/caspase-3 intrinsic pathway, accompanied by increased subG1 cell population.

What is the effect of combining patchouli alcohol with cisplatin?

Combining patchouli alcohol with cisplatin produced synergistic inhibitory activity in both A549 and A549/V16 cells, enhancing suppression of cancer cell proliferation.

Sep 24, 2026

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