Berberine inhibits human neuroblastoma cell growth through induction of p53-dependent apoptosis.
Berberine, an alkaloid, has anti-tumor properties in some cancer cells, but action mechanisms are not clear yet. We here investigated the anticancer activity of berberine and possible mechanisms in human neuroblastoma SK-N-SH and SK-N-MC cells. The p53-expressing cells, SK-N-SH (IC50=37 microM) were more susceptible to berberine than the p53-deficient cells, SK-N-MC (IC50 > or =100 microM) without cytotoxic effect on the cortical neuronal cells. Berberine caused cell cycle arrest in G0/G1 phase and apoptotic cell death, and these effects were much greater in SK-N-SH cells than those in SK-N-MC cells. Berberine much greatly decreased G0/G1 phase-associated cyclin and cyclin-dependent kinase (cyclin D1, cyclin E, Cdk2, and Cdk4) expression, and increased apoptotic gene expression and activation of caspase-3 in SK-N-SH cells. Exploration of p53 siRNA or pifithrin-alpha (PFT-alpha), a p53 inhibitor, in the SK-N-SH cells resulted in increase of IC50 values for cell viability, and decreased apoptotic cell death, expression of p53 and activation of caspase-3. Therefore, these results showed that berberine causes p53-dependent apoptotic death of neuroblastoma cells, and suggested that berberine may be useful as an anticancer agent for neuroblastoma.
Choi
Myoung Suk
MS
College of Pharmacy Medical Science and Engineering Research Center, Chungbuk National University 12, Gaeshin-dong, Heungduk-gu, Cheongju, Chungbuk 361-763, Korea.
Yuk
Dong Yeon
DY
Oh
Ju Hoon
JH
Jung
Hai Young
HY
Han
Sang Bae
SB
Moon
Dong Cheul
DC
Hong
Jin Tae
JT
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001599:Berberine / Q000494:pharmacology*; D048708:Cell Growth Processes / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D005260:Female; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D009447:Neuroblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
C494826:BAX protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D001599:Berberine