5-aminolevulinic acid induce apoptosis via NF-κB/JNK pathway in human oral cancer Ca9-22 cells

• Published in: Journal of oral pathology & medicine 2011-07, Vol.40 (6), p.483-489
• Main Authors: Chen, Hsin-Ming, Liu, Cheing-Meei, Yang, Hsiang, Chou, Han-Yi, Chiang, Chun-Pin, Kuo, Mark Yen-Ping
• Format: Article
• Language: English
• Subjects: Aminolevulinic Acid - pharmacology; Aminolevulinic Acid - therapeutic use; apoptosis; Apoptosis - drug effects; Biological and medical sciences; Caspase Inhibitors; Cell Line, Tumor; Dentistry; Fas-Associated Death Domain Protein - physiology; Humans; In Situ Nick-End Labeling; JNK; JNK Mitogen-Activated Protein Kinases - metabolism; MAP Kinase Signaling System - drug effects; Medical sciences; Mouth Neoplasms - drug therapy; NF-kappa B - metabolism; oral cancer; Otorhinolaryngology. Stomatology; Photochemotherapy; photodynamic therapy; RNA Interference; Tumors; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology
• ISSN: 0904-2512; 1600-0714
• DOI: 10.1111/j.1600-0714.2010.00973.x

J Oral Pathol Med (2010) 40: 483–489 Background:  5‐aminolevulinic acid‐based photodynamic therapy (5‐ALA‐PDT) is being used to treat oral pre‐cancerous and cancerous lesions with some encouraging clinical outcomes. However, the exact mechanisms behind the photodynamic treatment are still not fully elucidated. Method:  Flow cytometry, TdT‐mediated dUTP nick end labeling assay and Western blot analysis were used to investigate the effects of 5‐ALA‐PDT on human oral cancer Ca9–22 cells. Results:  We found that 5‐ALA‐PDT induces apoptosis in Ca9–22 cells. Western blotting showed that 5‐ALA‐PDT activates both the caspase‐8 and caspase‐9 pathways, which differed from previous studies conducted in other cell types. Activation of JNK was evident as early as 30 min. The caspases activation was inhibited by JNK inhibitor SP600125. Treatment with NF‐κB inhibitor Bay 11‐7082 (Bay) completely abrogated ALA‐PDT‐induced JNK activation. In addition, Bay and SP600125 almost completely abolished ALA‐PDT‐induced apoptosis. Conclusion:  These results demonstrate significant involvement of caspase‐8 and ‐9 and their upstream NF‐κB‐JNK pathways in ALA‐PDT‐induced apoptosis. Future studies on how NF‐κB and JNK activity regulate ALA‐PDT response should provide a better strategy for the treatment of oral cancer.