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

TL;DR

Alisol A, a natural compound, kills oral cancer cells by triggering apoptosis through the JNK/p38 MAPK signaling pathway.

Contribution

This study reveals a novel mechanism by which Alisol A induces apoptosis in oral cancer cells via JNK/p38 MAPK pathways.

Findings

Alisol A reduces oral cancer cell viability and induces apoptosis.

Activation of JNK and p38 MAPK pathways is crucial for Alisol A-induced apoptosis.

Alisol A modulates apoptotic proteins like HO-1, cIAP1, and XIAP.

Abstract

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.

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.

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.

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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