Modulation of apoptosis by berberine through inhibition of cyclooxygenase-2 and Mcl-1 expression in oral cancer cells.
BACKGROUND
We have previously shown that berberine exerts its anti-inflammatory effects through inhibition of cyclooxygenase-2 (COX-2) expression. In this study, we explored the biochemical influence of berberine-induced COX-2 reduction and apoptosis.


METHODS
KB cells were treated with berberine, and the apoptosis was measured by morphology and caspase-3 activity. The effects of prostaglandin E2 (PGE2) on berberine-mediated cell growth were also determined. The expression of COX-2, Bcl-2, Mcl-1, Akt and phosphorylated Akt in berberine-treated KB cells, with or without PGE2, were assessed by Western blots.


RESULTS
Berberine induced apoptosis in KB cells, and was partially reversed by incorporation of PGE2. 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 had no effect on total Akt, but slightly reversed the phosphorylated Akt, which was decreased by berberine.


CONCLUSIONS
These results suggest that berberine-induced apoptosis might be COX-2-dependent and is related to decreased Akt phosphorylation and Mcl-1 expression.
Kuo
Chi-Li
CL
Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan, Republic of China.
Chi
Chin-Wen
CW
Liu
Tsung-Yun
TY
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001599:Berberine / Q000494:pharmacology*; D002277:Carcinoma / Q000188:drug therapy / Q000473:pathology; D053148:Caspase 3; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007624:KB Cells; D008565:Membrane Proteins; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000473:pathology; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000187:drug effects / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors
D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D008565:Membrane Proteins; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D001599:Berberine; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D015232:Dinoprostone