Department of Biochemistry Institute of Biochemistry and Biophysics, University of Tehran, Enghelab Ave., P.O. Box: 13145-1384, Tehran, Iran.
Med Oncol. 2011 Dec;28(4):1577-83. doi: 10.1007/s12032-010-9586-0. Epub 2010 Jun 2.
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.
小檗碱是一种异喹啉生物碱，具有多种药理活性，包括抗炎和抗腹泻作用、诱导细胞凋亡和抗癌作用。据报道，小檗碱通过抑制核因子-κB（NF-κB）的表达发挥其抗炎作用。存活素和诱导型一氧化氮合酶（iNOS）蛋白可能与抗炎和抗凋亡功能之间的因果关系有关。为了研究小檗碱诱导细胞凋亡的机制，用不同浓度的小檗碱（25-100μM）处理人红白血病母细胞系（K562 细胞系）。在用 75μM 小檗碱处理 72 小时的细胞中观察到最显著的细胞生长停滞和凋亡作用。结果表明，小檗碱处理的细胞中存活素和 iNOS 蛋白水平降低。然而，iNOS 活性的降低并不影响细胞生长和凋亡。此外，向培养基中添加一氧化氮供体硝普钠可降低本细胞系中的细胞生长，但似乎其浓度太低，无法诱导细胞凋亡。因此，尽管 iNOS 在未处理的细胞中产生 NO，但在该细胞系中，NO 并未在致癌作用中发挥重要作用。这些结果表明，小檗碱的细胞凋亡活性可能是通过降低 K562 细胞中的存活素来介导的，但 iNOS 水平及其活性在小檗碱诱导的细胞凋亡中不起重要作用。
