BMI-1 is important in bufalin-induced apoptosis of K562 cells

Abstract

Abstract. The purpose of this study was to analyze the effects of bufalin on the gene expression of K562 cells and on the expression of BMI-1 pathway constituents in K562 cell apoptosis. K562 cells were treated with bufalin, and the inhibition rate and apoptosis were detected by an MTT assay, flow cytometry and a microarray assay. BMI-1, p16 INK4a and p14 ARF were examined by quantitative polymerase chain reaction (qPCR). Bufalin induced significant changes in the gene expression of the K562 cells; 4296 genes were differentially expressed, 2185 were upregulated and 2111 were downregulated. The most upregulated genes were associated with transcription regulation, while the most downregulated genes were associated with the non-coding RNA metabolic processes and DNA repair. qPCR analysis demonstrated that BMI-1 was overexpressed in the K562 cells. Bufalin is able to downregulate BMI-1 expression levels in K562 cells prematurely and cause an increase in the expression levels of p16 INK4a and p14 ARF . Moreover, bufalin downregulated BCR/ABL expression levels in a time-dependent manner, and the expression of BCR/ABL was not associated with the upregulation or downregulation of BMI-1 expression. Bufalin may induce K562 cell apoptosis by downregulating BMI-1 expression levels and accordingly upregulating the expression levels of p16 INK4a and p14 ARF . Bufalin may also induce K562 cell apoptosis via downregulating BCR/ABL expression levels, and this pathway may be independent of the BMI-1 pathway.

Cytochrome P450 Mining for Bufadienolide Diversification

“…Bufadienolides are a class of C24 steroids with a distinctive α-pyrone ring at the C17 position, which have attracted a lot of attention due to their excellent medical properties. In nature, they are mostly synthesized by toads and secreted through parotoid glands and cutaneous glands as a defensive weapon. − Bufadienolides are well known for their cardiotonic properties, and recently their anticancer activities have also attracted much attention. − In vitro cell experiments and in vivo animal models have shown that bufadienolides can effectively inhibit the cell proliferation of many types of tumors. − They are the major active ingredients of the Chinese medicine Chansu and Cinobufacini. − Now, Cinobufacini is one of the best-selling antitumor Chinese medicine in China.…”

Bufalin suppresses esophageal squamous cell carcinoma progression by activating the PIAS3/STAT3 signaling pathway

“…Studies have found that Bufalin is a broad-spectrum anti-tumor drug ( 23 ). At present, it has shown its anti-tumor activity in the clinical treatment of leukemia, liver cancer, gastric cancer and other tumors ( 24 , 25 ). A study has found that Bufalin can inhibit the proliferation of vascular endothelial cells in a variety of tumor tissues, affect its neovascularization, and then inhibit tumor growth ( 26 ).…”

“…A study has found that Bufalin can inhibit the proliferation of vascular endothelial cells in a variety of tumor tissues, affect its neovascularization, and then inhibit tumor growth ( 26 ). In leukemia-related study, it was found that Bufalin could significantly inhibit the growth of leukemic cells and induce their differentiation and apoptosis ( 25 ). Studies have shown that Bufalin can activate members of Caspase family and Bcl-2 family, promote the formation of Bax homodimer ( 27 ), and activate hydrolases such as Caspase-8, Caspase-9 and Caspase-3, which significantly increase the permeability of mitochondrial membrane and lead to the release of cytochrome C into the cytoplasm.…”