Protective Effect of Alpha-Linolenic Acid on Human Oral Squamous Cell Carcinoma Metastasis and Apoptotic Cell Death

• Published in: Nutrients Vol. 15; no. 23; p. 4992
• Main Authors: Su, Ching-Chyuan, Yu, Cheng-Chia, Shih, Yi-Wen, Liu, Kai-Li, Chen, Haw-Wen, Wu, Chih-Chung, Yang, Ya-Chen, Yeh, En-Ling, Li, Chien-Chun
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.12.2023
• Subjects: Adapter proteins; alpha-Linolenic Acid - pharmacology; Antibodies; Apoptosis; Biochemistry; Cancer; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - pathology; Care and treatment; Cell adhesion & migration; Cell death; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cytochrome; Cytochromes c; Enzymes; Epithelial-Mesenchymal Transition; Fatty acids; Head & neck cancer; Head and Neck Neoplasms; Humans; Hypoxia; Ligands; Linolenic acids; Medical prognosis; Membranes; Metabolism; Metabolites; Metastasis; Mitochondria; Monounsaturated fatty acids; Mortality; Mouth Neoplasms - drug therapy; Omega-3 fatty acids; Oral cancer; OSCC; Prognosis; Squamous cell carcinoma; Squamous Cell Carcinoma of Head and Neck; Tumor necrosis factor-TNF; Tumors; α-linolenic acid; Taiwan; United States > US; Japan; OSCC; epithelial–mesenchymal transition; apoptosis; metastasis; α-linolenic acid; oral cancer
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu15234992

Oral cancer ranks sixth among Taiwan's top 10 cancers and most patients with poor prognosis acquire metastases. The essential fatty acid alpha-linolenic acid (ALA) has been found to diminish many cancer properties. However, the anti-cancer activity of ALA in oral cancer has yet to be determined. We examined the mechanisms underlying ALA inhibition of metastasis and induction of apoptotic cell death in oral squamous cell carcinoma (OSCC). Migration and invasion assays confirmed the cancer cells' EMT capabilities, whereas flow cytometry and Western blotting identified molecular pathways in OSCC. ALA dramatically reduced cell growth in a concentration-dependent manner according to the findings. Low concentrations of ALA (100 or 200 μM) inhibit colony formation, the expression of Twist and EMT-related proteins, the expression of MMP2/-9 proteins, and enzyme activity, as well as cell migration and invasion. Treatment with high concentrations of ALA (200 or 400 μM) greatly increases JNK phosphorylation and c-jun nuclear accumulation and then upregulates the FasL/caspase8/caspase3 and Bid/cytochrome c/caspase9/caspase3 pathways, leading to cell death. Low concentrations of ALA inhibit SAS and GNM cell migration and invasion by suppressing Twist and downregulating EMT-related proteins or by decreasing the protein expression and enzyme activity of MMP-2/-9, whereas high concentrations of ALA promote apoptosis by activating the JNK/FasL/caspase 8/caspase 3-extrinsic pathway and the Bid/cytochrome c/caspase 9 pathway. ALA demonstrates potential as a treatment for OSCC patients.