Berberine Inhibits COX-2 Expression and Induces Apoptosis in Oral Cancer Cells

• Main Authors: Chi-Li Kuo, 郭啟利
• Other Authors: Tsung-Yun Liu
• Format: Others
• Language: en_US
• Published: 2004
• Online Access: http://ndltd.ncl.edu.tw/handle/26080155993251749508

博士 === 國立陽明大學 === 藥理學研究所 === 92 === Berberine, an isoquinoline alkaloid, has a wide range of pharmacological effects, including anti-inflammation, yet the exact mechanism is unknown. Because cyclooxygenase-2 (COX-2) plays a key role in prostaglandins (PGs) synthesis which is elevated in inflammation, this thesis examined whether the anti-inflammatory mechanism of berberine is mediated through COX-2 regulation. In oral cancer cell line OC2 and KB cells, a 12 hr berberine treatment (1, 10, and 100 μM) reduced prostaglandin E2 (PGE2) production dose-dependently with or without 12-O-tetradecanoylphorbol-13-acetate (TPA, 10 nM) induction. This berberine induced effect occurred rapidly in 3 hr treatment as a result of reduced COX-2 protein, but not enzyme activity. The electrophoretic mobility shift assay (EMSA) revealed that activator protein 1 (AP-1) binding was decreased in oral cancer cells treated with berberine for 2 hr. Further analysis showed that berberine inhibited AP-1 binding directly. These anti-inflammatory effects paralleled to the in vivo results where berberine pretreatment of Wistar rat inhibited the production of exudates and PGE2 in carrageenan induced air pouch. Biochemical influence of berberine-induced COX-2 reduction and apoptosis was also explored. Berberine induced apoptosis in KB cells after 12 hr treatment, and was partially reversed by incorporation of PGE2. A three hour and 6 hr berberine treatment inhibited COX-2 and MCL-1 expression dose-dependently but not BCL-2. PGE2 induced COX-2 and MCL-1 expression and reversed the repressive effect of berberine on MCL-1. In addition, PGE2 treatment had no effect on the total level of AKT, but slightly reversed the phosphorylated AKT, which were decreased by berberine. These results suggest that berberine-induced apoptosis might be COX-2 dependent and are related to decreased AKT phosphorylation and MCL-1 expression.