Open Access

ARTICLE

Alisol A Exerts Anti-Proliferative Activity against Human Oral Cancer Cells through Triggering JNK/p38 MAPK-Mediated Apoptotic Cascade

Yi-Tzu Chen^1,2,3,#, Shao-Hsuan Kao^4,5,#, Chun-Yi Chuang^6,7, Chun-Wen Su^4,5, Wei-En Yang^4,5, Chih-Hsin Tang^8,9,10, Shun-Fa Yang^4,5,*, Chiao-Wen Lin^2,3,*

1 School of Dentistry, Chung Shan Medical University, Taichung, 402, Taiwan
2 Institute of Oral Sciences, Chung Shan Medical University, Taichung, 402, Taiwan
3 Department of Dentistry, Chung Shan Medical University Hospital, Taichung, 402, Taiwan
4 Institute of Medicine, Chung Shan Medical University, Taichung, 402, Taiwan
5 Department of Medical Research, Chung Shan Medical University Hospital, Taichung, 402, Taiwan
6 School of Medicine, Chung Shan Medical University, Taichung, 402, Taiwan
7 Department of Otolaryngology, Chung Shan Medical University Hospital, Taichung, 402, Taiwan
8 Department of Pharmacology, School of Medicine, China Medical University, Taichung, 404, Taiwan
9 Department of Medical Laboratory Science and Biotechnology, Asia University, Taichung, 413, Taiwan
10 Chinese Medicine Research Center, China Medical University, Taichung, 404, Taiwan

* Corresponding Authors: Shun-Fa Yang. Email: ; Chiao-Wen Lin. Email:
# These authors contributed equally to this work

Oncology Research 2025, 33(11), 3387-3404. https://doi.org/10.32604/or.2025.069877

Received 02 July 2025; Accepted 04 September 2025; Issue published 22 October 2025

Abstract

Background: Alisol A is a natural compound isolated from Alismatis Rhizoma, known for its diverse pharmacological activities, including anticancer and neuroprotective effects. This study aimed to explore the anticancer effects of Alisol A on oral cancer cells and elucidate its underlying mechanisms. Methods: Cell viability was measured by MTT assay, cell cycle by flow cytometry, and apoptosis by Annexin V/PI staining and caspase activation. Regulation of signaling pathways was analyzed using an apoptosis-related protein array, immunoblotting, and specific kinase inhibitors. Results: Alisol A reduced the viability of oral cancer cell lines, induced sub-G1 phase accumulation, and augmented the number of apoptotic cells. Protein array results indicated that Alisol A enhanced the expression of heme oxygenase-1 (HO-1), while suppressing cellular inhibitor of apoptosis protein 1 (cIAP1) and X-linked inhibitor of apoptosis protein (XIAP) levels in SCC-9 cells. These changes were further confirmed in both SCC-9 and HSC-3 cells by immunoblotting. In addition, Alisol A triggered the activation of caspase-8, -9, and -3, as well as poly (ADP-ribose) polymerase (PARP) cleavage in both cell lines. Analysis of signaling pathways showed that mitogen-activated protein kinases (MAPKs) were significantly activated by Alisol A. Notably, inhibition of JNK and p38 markedly reduced Alisol A-induced activation of caspase-8, -9, and -3. Conclusions: Our findings demonstrate that Alisol A exerts potent anticancer effects on oral cancer cells by inducing caspase-dependent apoptosis via activation of the JNK and p38 signaling pathways. These results suggest that Alisol A may have therapeutic potential for the treatment of oral cancer.

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