Open Access

ARTICLE

Synergistic Anti-Lung Cancer and Immunomodulatory Effects of Combined Extracts from Acanthopanax sessiliflorus, Phragmites communis, and Pinus densiflora

Anjali Kariyarath Valappil^1,#, Reshmi Akter^2,#, Muhammad Awais², Dong Uk Yang³, Daehyo Jung², Li Ling⁴, Eun Kim⁵, Kyu Hyeong Yoon⁵, Yoon Ok Lee⁵, Deok Chun Yang^1,2,4,*

1 Department of Biopharmaceutical Biotechnology, College of Life Science, Kyung Hee University, Yongin-si, 17104, Republic of Korea
2 Graduate School of Biotechnology, College of Life Sciences, Kyung Hee University, Yongin-si, 17104, Republic of Korea
3 AIBIOME, 6, Jeonmin-ro 30beon-gil, Yuseong-gu, Daejeon, 34214, Republic of Korea
4 Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun, 130117, China
5 Genome and Natural Bio. 3F, Jinhwan bldg, 81, Hancheon-ro 2-gil, Dongdaemun-gu, Seoul, 02634, Republic of Korea

* Corresponding Author: Deok Chun Yang. Email:
# These authors contributed equally to this work

(This article belongs to the Special Issue: Natural Product-Based Anticancer Drug Discovery)

BIOCELL 2025, 49(9), 1771-1795. https://doi.org/10.32604/biocell.2025.069145

Received 16 June 2025; Accepted 11 August 2025; Issue published 25 September 2025

Abstract

Objectives: The phytochemical investigation of traditional herbal medicines holds significant promise for modern drug discovery, particularly in cancer therapy. This study aimed to evaluate the cytotoxicity, apoptosis induction, and immune-modulatory activities of extracts from three herbal medicines with historical use in traditional medicine—Acanthopanax sessiliflorus, Phragmites communis, and Pinus densiflora, as well as their combined extract (GMAS 01/COM), on human lung cancer cells (A549) and normal cell lines, including murine macrophages (RAW 264.7) and human keratinocytes (HaCaT). Methods: Plant extracts were prepared using aqueous extraction, sonication, and rotary evaporation. The total phenolic and flavonoid contents were quantified using the Folin-Ciocalteu and AlCl₃ colorimetric methods, respectively. Antioxidant potential was evaluated via 2,2-Diphenyl-1-picrylhydrazyl (DPPH) scavenging and reducing power assays. Cytotoxicity was assessed using an MTT assay, while reactive oxygen species (ROS) generation was quantified using a 2^′,7^′-Dichlorodihydrofluorescein diacetate (DCFH-DA) assay. Anticancer properties, including colony formation inhibition and migration suppression, were examined using colony formation and wound healing assays. The expression of apoptotic and inflammatory mediators was analysed through qPCR. Results: GMAS 01 selectively induced apoptosis in A549 cells without cytotoxic effects on RAW264.7 and HaCaT cells. Mechanistically, it elevated intracellular ROS and activated the intrinsic mitochondrial apoptotic pathway, evidenced by p53 upregulation, increased Bax, and decreased Bcl-2 expression. GMAS 01 also significantly inhibited colony formation and migration in A549 cells. In RAW264.7 cells, it reduced nitric oxide (NO) production and downregulated iNOS, COX-2, IL-6, and IL-8, indicating strong immunomodulatory activity. Conclusion: GMAS 01 exhibits potent antioxidant, anti-inflammatory, and anticancer effects, likely mediated through ROS-induced mitochondrial apoptosis. However, mechanistic interpretations are limited by the absence of protein-level validation and pathway inhibition studies. Upcoming studies should aim to verify the underlying mechanisms and evaluate their potential for real-world application.

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