Polyphyllin D induces apoptosis and differentiation in K562 human leukemia cells.

Polyphyllin D, a compound derived from Paris polyphylla rhizoma, demonstrated strong anticancer activities in a previous study. Our results demonstrated that polyphyllin D exerts a growth inhibitory effect by inducing apoptosis and differentiation in the human erythroleukemia cell line K562. Polyphyllin D induced apoptosis via the mitochondrial apoptotic pathway, as evidenced by the decreased Bcl-2 and Bcr/Abl expression levels, the disruption of MMP and increased Bax, cytochrome c and cleaved-caspase-3 levels. At a low dose, polyphyllin D increased CD14 expression on the surface of K562 cells and induced cells to differentiate into monocytes or mature macrophages. These data suggest that polyphyllin D has the potential to be a potent therapeutic agent for treating human chronic myelogenous leukemia.

Acarbose treatment affects the serum levels of inflammatory cytokines and the gut content of bifidobacteria in Chinese patients with type 2 diabetes mellitus.

BACKGROUND: The effects of acarbose add-on therapy on gut microbiota and inflammatory cytokines were investigated in Chinese patients with type 2 diabetes mellitus (DM). METHODS: Ninety-five DM patients were randomly allocated to two groups: 59 to Group A who received antidiabetic treatment that included acarbose 150 mg/day, and 36 to Group B who received similar treatment to Group A but without acarbose. Forty-five healthy volunteers were selected as a control group. Serum concentrations of inflammatory cytokines were determined by ELISA, and the contents of 16S rDNA of gut bacteria were determined by real-time quantitative polymerase chain reaction. General linear analysis for repeated measurements was used to analyze trend differences between the two diabetic groups. RESULTS: After 4 weeks of antidiabetic treatment, the gut contents of Bifidobacterium longum and Enterococcus faecalis were significantly increased in both diabetes groups. The increase of Bifidobacterium longum (P = 0.004) and the decrease of lipopolysaccharides (LPS) (P < 0.001) and prothrombin activator inhibitor-1 (P = 0.003) were more significant in Group A. Decreases of monocyte chemoattractant protein-1 and LPS were more significant in patients whose HbA1c decrease was ≥1%, but there were no significant differences in the changes of other cytokines and gut bacteria between patients with HbA1c <7% and ≥7%. Pearson correlation analysis showed that changes of Enterococcus faecalis were negatively correlated with LPS, while multiple linear regression analysis showed a positive correlation of Bifidobacterium longum with acarbose treatment and the high-density lipoprotein cholesterol concentration. CONCLUSIONS: Acarbose treatment can increase the content of gut Bifidobacterium longum in type 2 diabetes mellitus patients and decrease some inflammatory cytokines independently of its antihyperglycemic effects.

Growth inhibition effects of isoalantolactone on K562/A02 cells: caspase-dependent apoptotic pathways, S phase arrest, and downregulation of Bcr/Abl.

Isoalantolactone, a sesquiterpene lactone, is the active component of Inula helenium (Compositae). It has been reported that isoalantolactone has the capacity to inhibit tumor cell growth through induction of apoptosis. The purposes of this study were to evaluate the effects of isoalantolactone on the human erythroleukemia drug-resistant cell line K562/A02 and to provide evidence of its function as a potent therapeutic agent in patients with chronic myelogenous leukemia with the Bcr/Abl phenotype. Our results showed that isoalantolactone significantly inhibited K562/A02 cell growth by downregulating Bcr/Abl expression. Isoalantolactone also induced apoptosis via increase generation of reactive oxygen species, modulation of the protein levels of Bcl-2 family members, caspase activation, poly ADP-ribose polymerase (PARP) cleavage, and release of cytochrome c. We also observed that isoalantolactone inhibited proliferation by inducing cell cycle arrest in the S phase. Taken together, all these findings support that growth inhibition effects of isoalantolactone on K562/A02 cells may be mediated through caspase-dependent apoptotic pathways, S phase arrest, and downregulation of Bcr/Abl.

Alantolactone inhibits growth of K562/adriamycin cells by downregulating Bcr/Abl and P-glycoprotein expression.

Alantolactone, a sesquiterpene lactone containing an α-methylene-γ-lactone group, is the active component of Inula helenium (Compositae), a traditional Chinese medicinal herb. It has been reported that alantolactone has the capacity to inhibit tumor cell growth through induction of apoptosis. The purpose of this study was to assess the effects of alantolactone in the adriamycin (ADR)-resistant human erythroleukemia cell line K562/ADR, and provide evidence that it might function as a potent therapeutic agent in chronic myelogenous leukemia (CML) patients with Bcr/Abl and the multidrug-resistance phenotype. Our results showed that alantolactone significantly inhibited K562/ADR cell growth by downregulating Bcr/Abl and P-glycoprotein expression. Alantolactone also induced apoptosis via modulation of protein levels of Bcl-2 family members, caspase activation, poly ADP ribose polymerase cleavage, and cytochrome C release. We also observed that alantolactone induced cell-cycle arrest in the G2/M phase, downregulated cyclin B1 and cyclin-dependent protein kinase 1, and upregulated the cyclin-dependent kinase inhibitor p21. Together, these results demonstrate that alantolactone may be a potent therapeutic agent against CML, and a potential Bcr/Abl inhibitor.