Emodin Induces Apoptosis of K562/Adr Cells Probably through Akt-Caspase 3 Signal Pathway / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the apoptosis-inducing effects of emodin on multidrug resistant leukemia cell line K562/Adr, and to explore the role of Akt-Caspase 3 signal pathway in apoptosis of K562/Adr cells treated with emodin.</p><p><b>METHODS</b>K562/Adr cells were exposed to emodin of different doses. The ability of emodin to induce apoptosis of K562/Adr cells was detected by Annexin V/PI double labeled flow cytometry and DNA ploidy analysis, the expressions of procaspase-3, PARP, Akt, p-Akt protein were determined by Western blot.</p><p><b>RESULTS</b>Apoptosis in K562/Adr cells could be induced by emodin in a dose dependent manner, Western blot results showed that emodin down-regulated the expression levels of procaspase-3, Akt, p-Akt, PARA 116 KD in treated K562/Adr cells, up-regulated expressions leves of PARP 85 KD in a time-dependent manner.</p><p><b>CONCLUSION</b>The Akt-Caspase 3 signal pathway may be involved in these processes.</p>

Effect of emodin on proliferation inhibition and apoptosis induction in leukemic K562 cells / 中国实验血液学杂志

The study was aimed to investigate the effects of emodin on proliferation inhibition and apoptosis induction in human chronic myeloid leukemia cell line K562 cells, and to explore the role of P210 protein and activation of caspase 3 in these processes. K562 cells were exposed to emodin at different doses. The proliferation inhibition was detected by MTT assay and colony formation test. The ability of emodin to induce apoptosis and DNA fragmentation were examined by flow cytometry. The expressions of P210, procaspase-3 and PARP protein were determined by Western blot. The results indicated that the emodin remarkably inhibited the K562 cell proliferation, with IC(50) value of 38.25 micromol/L after treatment for 48 hours. Meanwhile induced apoptosis, Annexin V-FITC positive cells, sub-G(1) apoptotic peak and DNA fragmentation in K562 cells confirmed that emodin induced apoptosis in K562 cells in dose-dependent manner. Western blot results showed that emodin inhibited phosphorylation of P210 protein in K562 cells and down-regulated the expression levels of P210. The procaspase-3 level in treated K562 cells decreased with increased expressions of PARP in time-dependent manner. It is concluded that the emodin efficiently inhibits growth and induces apoptosis of K562 cells, while the inhibition of phosphorylation of P210 protein, down-regulation of P210 protein expression and activation of caspase-3 may be involved in these processes.

Emodin induces leukemic HL-60 cells apoptosis probably by inhibiting Akt signal pathway / 药学学报

This study is to investigate the effect of emodin on inducing human myeloid leukemia cell line HL-60 apoptosis and the role of Akt signal pathway in the apoptosis. HL-60 cells were exposed to various dosages of emodin. MTT assay was used to detect HL-60 cell proliferation. Distribution of HL-60 cells in cell cycle was analyzed by flow cytometry and cell apoptosis was observed by MitoCapture apoptosis detection. The protein expressions of Akt signal pathway were detected by Western blotting. The result showed that emodin remarkably inhibited the cell proliferation. The IC50 value for 48 h treatment was about 20 micromol x L(-1). Apoptosis in HL-60 cells could be efficiently induced by emodin in a dose dependent manner and cells were arrested at G0/G1. The expressions of Akt, p-Akt, IkappaB-alpha, p-IkappaB-alpha, p65, p-p65, mTOR and p-mTOR in Akt signal pathway were downregulated after emodin treatment. It can be concluded that emodin could efficiently induce growth inhibition and apoptosis in HL-60 cells. Akt signal pathway may be involved in this process.

Inhibitory effects of emodin on drug-resistant HL-60/ADR cell proliferation and its induction of apoptosis / 中国实验血液学杂志

The study was aimed to investigate the effects of emodin on the proliferation and apoptosis of adriamycin-resistant HL-60/ADR cells, and to explore the underlying mechanism. The cell viability and colony formation were detected by MTT assay and colony formation assay respectively. Apoptotic cells were tested by means of cell cycle analysis, mitochondrial transmembrane potential levels, caspase-3 activity detection, Annexin V FITC/PI staining and TUNEL labeling. RT-PCR was used to analyze the bcl-2 and c-myc mRNA expressions. The protein expressions of Bcl-2, c-Myc and caspase-3 precursor were determined by Western blot. The results showed that HL-60/ADR cell growth was significantly inhibited by emodin in dose and time dependent manners. Cell colony formation obviously decreased with IC50 5.79 micromol/L. G0/G1 phase cell population increased while G2/M phase cells decreased in 40 and 80 micromol/L groups compared with control group (p < 0.01), and no significant difference of cell cycle was observed in 20 micromol/L group (p > 0.05). The typical hypo-diploid peak (apoptotic peak) appeared in each dose group. The levels of mitochondrial transmembrane potential of HL-60/ADR cells decreased and caspase-3 activity increased when incubated with emodin for 12 and 24 hours respectively. Apoptosis occurred in a dose-dependent manner, and its earlier and later stages were identified by Annexin-V FITC/PI staining and TUNEL labeling methods respectively. The expressions of bcl-2, c-myc mRNA and Bcl-2, c-Myc, caspase-3 precursor protein were all down-regulated in a time-dependent manner after treatment with emodin at different times. It is concluded that emodin efficiently inhibits growth and induces apoptosis on HL-60/ADR cells, which may be related with the down-regulation of mitochondrial transmembrane potential and expressions of bcl-2 and c-myc, as well as up-regulation of caspase-3 activity.