Berberine-induced apoptosis via decreasing the survivin protein in K562 cell line

Abstract

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.

Calprotectin induces cell death in human prostate cancer cell (LNCaP) through survivin protein alteration

“…Survivin is an anti‐apoptotic protein, overexpression of survivin was observed in several tumor cells (Altieri, ; Altieri, ; Pazhang et al, ). To further dissect the possible CP mechanism of action, the survivin protein level in treated and untreated LNCaP cells was evaluated by immunocytochemistry and immunoblotting techniques.…”

“…Survivin is a bifunctional inhibitor of apoptosis (IAP) that has been implicated in the protection against apoptosis and promoting mitosis (Dohi et al, ). It is well‐established that survivin is expressed in most human cancers and has recently attracted a great attention as a potential candidate for cancer therapy (Altieri, ; Altieri, ; Pazhang et al, ). Moreover, it is determined that survivin mediates resistance to antiandrogen therapy in prostate cancer cell lines including LNCaP, PC‐3, and DU‐145 and interestingly all three cell lines were found to strongly express survivin.…”

Apoptotic effect of berberine via Bcl‐2, ROR1, and mir‐21 in patients with B‐chronic lymphocytic leukemia

“…In this way, one study demonstrated that berberine induced apoptosis in breast, liver, and hematopoietic cancer cells through mitochondrial‐dependent manner by increasing levels of caspase‐3 and 8 activity and decreasing expression of caspase inhibitors such as survivin and Bcl‐2 (Marschitz et al, 2000; Patil, Kim, & Jayaprakasha, 2010; Pazhang, Ahmadian, Mahmoudian, & Shafiezadeh, 2011; Yip & Ho, 2013). Furthermore, results demonstrated that berberine leads to up‐regulation of p53 as an apoptotic inducer protein, while without affecting the normal breast epithelial cell growth at 25 μM concentration (Patil et al, 2010).…”

Berberine Inhibits FoxM1 Dependent Transcriptional Regulation of POLE2 and Interferes with the Survival of Lung Adenocarcinoma

“…Berberine has low toxicity to healthy cells and high cytotoxicity to cancer cells, which makes its research in anticancer become the most promising. Since the rst study on the cytotoxicity in cancer cells of berberine in 1986 7 , its anticancer properties have been proved in many cancer cell studies [8][9][10][11][12] , which makes berberine one of the most interesting and promising natural anticancer drugs.…”