@Article{or.2025.069877,
AUTHOR = {Yi-Tzu Chen, Shao-Hsuan Kao, Chun-Yi Chuang, Chun-Wen Su, Wei-En Yang, Chih-Hsin Tang, Shun-Fa Yang, Chiao-Wen Lin},
TITLE = {Alisol A Exerts Anti-Proliferative Activity against Human Oral Cancer Cells through Triggering JNK/p38 MAPK-Mediated Apoptotic Cascade},
JOURNAL = {Oncology Research},
VOLUME = {33},
YEAR = {2025},
NUMBER = {11},
PAGES = {3387--3404},
URL = {http://www.techscience.com/or/v33n11/64080},
ISSN = {1555-3906},
ABSTRACT = { <b>Background:</b> Alisol A is a natural compound isolated from <i>Alismatis Rhizoma</i>, 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. <b>Methods:</b> 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. <b>Results:</b> 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. <b>Conclusions:</b> 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.},
DOI = {10.32604/or.2025.069877}
}