Berberine Inhibits Human Neuroblastoma Cell Growth through Induction of p53-dependent Apoptosis

• Published in: Anticancer research 2008-11, Vol.28 (6A), p.3777-3784
• Main Authors: Choi, Myoung Suk, Yuk, Dong Yeon, Oh, Ju Hoon, Jung, Hai Young, Han, Sang Bae, Moon, Dong Cheul, Hong, Jin Tae
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - drug effects; Apoptosis - physiology; bcl-2-Associated X Protein - biosynthesis; Berberine - pharmacology; Biological and medical sciences; Cell Growth Processes - drug effects; Cell Growth Processes - physiology; Cell Line, Tumor; Cell Nucleus - metabolism; Female; G1 Phase - drug effects; Humans; Medical sciences; Neuroblastoma - drug therapy; Neuroblastoma - metabolism; Neuroblastoma - pathology; Neurology; Pregnancy; Proto-Oncogene Proteins c-bcl-2 - biosynthesis; Rats; Rats, Sprague-Dawley; Resting Phase, Cell Cycle - drug effects; Tumor Suppressor Protein p53 - metabolism; Tumors; Tumors of the nervous system. Phacomatoses
• ISSN: 0250-7005; 1791-7530

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 (IC 50 =37 μM) were more susceptible to berberine than the p53-deficient cells, SK-N-MC (IC 50 ≥100 μM) without cytotoxic effect on the cortical neuronal cells. Berberine caused cell cycle arrest in G 0 /G 1 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 G 0 /G 1 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-α (PFT-α), a p53 inhibitor, in the SK-N-SH cells resulted in increase of IC 50 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.