p38 MAPK and NF-κB pathways are involved in naphtho[1,2-b] furan-4,5-dione induced anti-proliferation and apoptosis of human hepatoma cells

• Published in: Cancer letters 2010-09, Vol.295 (1), p.92-99
• Main Authors: Chiu, Chien-Chih, Chen, Jeff Yi-Fu, Lin, Kuwi-Li, Huang, Chi-Jung, Lee, Jin-Ching, Chen, Bin-Hung, Chen, Wan-Yu, Lo, Yi-Han, Chen, Yi-Lan, Tseng, Chih-Hua, Chen, Yeh-Long, Lin, Shinne-Ren
• Format: Article
• Language: English
• Subjects: Hematology, Oncology and Palliative Medicine; Hepatocellular carcinoma (HCC); Naphthoquinone; NF-κB; p38 MAPK
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2010.02.017

Abstract Naphtho[1,2-b] furan-4,5-dione (NFD) was investigated for its anti-proliferation effect on human hepatocellular carcinoma (HCC), Hep3B, HepG2 , and Huh-7 cells. The effect of NFD on inhibiting proliferation and apoptosis was correlated with up-regulation of pro-apoptotic protein and down-regulation of pro-survival proteins. Remarkably, we found that NFD inhibited the nuclear translocation of NF-κB, likely accounting for the down-regulation of pro-survival Bcl-2 family. Furthermore, suppression of p38 MAPK activity by a specific inhibitor significantly rescued the cell proliferation inhibited by NFD. These findings suggest that signaling imbalance between p38 MAPK and NF-κB by NFD results in the proliferative inhibition and apoptosis of HCC tumor cells.