Berberine-induced apoptosis via decreasing the survivin protein in K562 cell line.
Berberine is an isoquinoline alkaloid with multiple pharmacological activities, including anti-inflammatory and anti-diarrhea effect, the induction of apoptosis and anti-cancer effect. It has been reported that berberine exerts its anti-inflammatory effect via suppressing nuclear factor-kappa B (NF-κB) expression. Survivin and inducible nitric oxide synthase (iNOS) proteins may contribute to the causal relationship between anti-inflammatory and anti-apoptotic function. To investigate the mechanism of berberine-induced apoptotic activities, the human erythro-myeloblastoid leukemia cell line (K562 cell line) was treated with different concentrations of berberine (25-100 μM). The most significant cellular growth arrest and apoptotic effects were observed in the cells treated with 75 μM of berberine for 72 h. The results indicate that survivin and iNOS protein levels were decreased in berberine-treated cells. However, decrease in the iNOS activity did not affect the cell growth and apoptosis. Moreover, the addition of NO donor, sodium nitroprusside, to culture medium decreased the cell growth in the present cell line, but it seemed that its concentration was too low to induce apoptosis. So despite its production by iNOS in untreated cells, NO does not play a significant role in carcinogenesis in this cell line. These results indicate that the apoptotic activity of berberine may be mediated through the reduction of survivin in K562 cells, but iNOS level and its activity does not play a significant role in berberine-induced apoptosis.
Department of Biochemistry Institute of Biochemistry and Biophysics, University of Tehran, Enghelab Ave., P.O. Box: 13145-1384, Tehran, Iran.
Yaghub
Y
Pazhang
Shahin
S
Ahmadian
Massoud
M
Mahmoudian
Mahshid
M
Shafiezadeh
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001599:Berberine / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D015151:Immunoblotting; D051034:Inhibitor of Apoptosis Proteins / Q000096:biosynthesis*; D020014:K562 Cells; D008856:Microscopy, Fluorescence; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D000077022:Survivin
D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin; D001599:Berberine; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II