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


METHODS
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.


CONCLUSIONS
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.
School of Dentistry, College of Medicine, National Taiwan University, Taipei, Taiwan.
Hsin-Ming
HM
Chen
Cheing-Meei
CM
Liu
Hsiang
H
Yang
Han-Yi
HY
Chou
Chun-Pin
CP
Chiang
Mark Yen-Ping
MY
Kuo
D000622:Aminolevulinic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D061945:Caspase Inhibitors; D045744:Cell Line, Tumor; D053200:Fas-Associated Death Domain Protein / Q000502:physiology; D006801:Humans; D020287:In Situ Nick-End Labeling; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009062:Mouth Neoplasms / Q000188:drug therapy*; D016328:NF-kappa B / Q000378:metabolism*; D010778:Photochemotherapy; D034622:RNA Interference
D061945:Caspase Inhibitors; D053200:Fas-Associated Death Domain Protein; D016328:NF-kappa B; D000622:Aminolevulinic Acid; D048031:JNK Mitogen-Activated Protein Kinases