β-sitosterol suppresses fibroblast growth factor and epidermal growth factor receptors to induce apoptosis and inhibit migration in lung cancer: an in vitro study

Shun-An Kan; Musarat Hussain; Chikondi Jassi; Wei-Wen Kuo; Chia-Hua Kuo; Pei-Ying Pai; Shu-Hui Lin; Yueh-Min Lin; Chih-Yang Huang; Shinn-Zong Lin

doi:10.62347/NZCG1179

β-sitosterol suppresses fibroblast growth factor and epidermal growth factor receptors to induce apoptosis and inhibit migration in lung cancer: an in vitro study

Am J Cancer Res. 2025 Mar 15;15(3):1109-1121. doi: 10.62347/NZCG1179. eCollection 2025.

Authors

Shun-An Kan¹, Musarat Hussain², Chikondi Jassi³, Wei-Wen Kuo^{2

4

5}, Chia-Hua Kuo^{6

7}, Pei-Ying Pai^{8

9}, Shu-Hui Lin^{10

11

12}, Yueh-Min Lin^{13

14}, Chih-Yang Huang^{3

15

16

17

18}, Shinn-Zong Lin^{19

20}

Affiliations

¹ Taipei Veterans General Hospital Taipei 112, Taiwan.
² Department of Biological Science and Technology, China Medical University Taichung 40402, Taiwan.
³ Cardiovascular and Mitochondrial Related Diseases Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation Hualien 970, Taiwan.
⁴ Ph.D. Program for Biotechnology Industry, China Medical University Taichung 40402, Taiwan.
⁵ School of Pharmacy, China Medical University Taichung 40402, Taiwan.
⁶ Laboratory of Exercise Biochemistry, University of Taipei Taipei 11153, Taiwan.
⁷ School of Physical Education and Sports Science, Soochow University Suzhou 215021, Jiangsu, China.
⁸ School of Medicine, College of Medicine, China Medical University Taichung 40402, Taiwan.
⁹ Division of Cardiovascular Medicine, Department of Medicine, China Medical University Hospital Taichung 40447, Taiwan.
¹⁰ Department of Surgical Pathology, Changhua Christian Hospital Changhua 50094, Taiwan.
¹¹ Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University Taichung 400, Taiwan.
¹² Department of Medical Laboratory Science and Biotechnology, Central Taiwan University of Science and Technology Taichung 40601, Taiwan.
¹³ Department of Pathology, Changhua Christian Hospital Changhua 500209, Taiwan.
¹⁴ School of Medicine, Chung Shan Medical University Taichung 402, Taiwan.
¹⁵ Department of Medical Research, China Medical University Hospital, China Medical University Taichung 40402, Taiwan.
¹⁶ Department of Biotechnology, Asia University Taichung 413305, Taiwan.
¹⁷ Center of General Education, Buddhist Tzu Chi Medical Foundation, Tzu Chi University of Science and Technology Hualien 970, Taiwan.
¹⁸ Graduate Institute of Biomedical Sciences, China Medical University Taichung 404, Taiwan.
¹⁹ Bioinnovation Center, Buddhist Tzu Chi Medical Foundation Hualien 970, Taiwan.
²⁰ Department of Neurosurgery, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation Hualien 970, Taiwan.

Abstract

β-Sitosterol (BS), is a significant bioactive component of phytosterols found in plants, foods, and dietary supplements. Its nutritional benefits include lowering of cholesterol levels, boost immune system as well as reduce inflammation. Previous studies have demonstrated its significant anticancer effects across various human cancers. However, the specific mechanisms of action of BS in lung cancer remain unclear. This study aimed to investigate the mechanisms through which BS exerts its anticancer properties in human lung cancer cells, focusing on its anti-proliferative, apoptotic, cytotoxic, and anti-migratory effects. We conducted an in vitro study to assess the effects of BS on lung cancer cell lines A549 and H1975. We used a range of assays, including MTT, western blot, wound healing, transwell migration, immunofluorescence, TUNEL, and cell survival assays, to evaluate the impact of BS on cell proliferation, apoptosis, cytotoxicity, and migration. Our findings indicate that BS inhibits the proliferation of lung cancer cells in a time- and dose-dependent manner. It significantly promotes apoptosis and impairs both cancer cell migration and survival. Additionally, BS suppresses the expression of both fibroblast growth factor receptor-1 (FGFR1) and epidermal growth factor (EGFR), leading to the downregulation of the PI3K/AKT/mTOR/CD1 signaling pathway. BS demonstrates significant anticancer potential in lung cancer cells by inhibiting proliferation, inducing apoptosis, and reducing cell migration. These effects are likely mediated by the concurrent downregulation of FGFR1 and EGFR, leading to the inhibition of the PI3K/AKT/mTOR/CD1 signaling pathway, thereby warranting further investigation of BS as a potential therapeutic agent for lung cancer.

Keywords: Apoptosis; epidermal growth factor receptor; fibroblast growth factor receptor 1; lung cancer; β-Sitosterol (BS).