Arsenic disulfide-triggered apoptosis and erythroid differentiation in myelodysplastic syndrome and acute myeloid leukemia cell lines.

OBJECTIVES: Effects of arsenic disulfide (As2S2) were investigated by focusing on growth inhibition, apoptosis induction, and erythroid differentiation in MDS-L, F-36p and HL-60 cells, derived from myelodysplastic syndrome (MDS), MDS/acute myeloid leukemia (AML), and de novo AML, respectively. METHODS: Cell viability was determined by MTT assay. Apoptosis induction was analyzed using Annexin V/propidium iodide staining. Erythroid differentiation was assessed by the expression level of CD235a, a marker for detection of the erythroid cell lineage. The activation of p38 MAPK and the expression profile of apoptosis-related proteins Bcl-2 and Bid were analyzed using western blot. RESULTS: As2S2 inhibited cell growth of these cell lines. Of note, the IC50 value of As2S2 in MDS-L cells was comparable to that in F-36p cells, and was half of that in HL-60 cells. A dose-dependent decrease in cell viability and concomitant increase in the percentage of apoptotic cells were observed in F-36p cells treated with 8 and 16 µM As2S2 for 72 hours. However, similar phenomena were only observed in HL-60 cells when treated with as high as 16 µM As2S2. Furthermore, As2S2 exerted more potent erythroid differentiation-inducing activity on F-36p cells than HL-60 cells. Interestingly, negative correlation between p38 MAPK signaling pathway and As2S2-induced erythroid differentiation was observed in HL-60 cells. Treatment with relatively high concentration of As2S2 resulted in the downregulation of Bcl-2 and Bid proteins in HL-60 cells. DISCUSSION: These results suggest that compared to AML cell line, MDS and MDS/AML cell lines are more sensitive to not only the erythroid differentiation-inducing activity of As2S2, but also its cytotoxicity associated with apoptosis induction. These findings further provide novel insight into As2S2 action toward its use for clinical application in patients with hematological disorders.

[Study on antiinflammatory effect of different chemotype of Cinnamomum camphora on rat arthritis model induced by Freund's adjuvant].

OBJECTIVE: To study the antiinflammatory effects of naphtha from different chemotypes of Cinnamomum camphora and natural borneol on the rat arthritis model induced by Freund's adjuvant. METHOD: The arthritis model was induced by injecting Freund's adjuvant in rat voix pedis dermis and the rats were randomly divided into seven groups: normal control group, model control group, triptergium wilfordii control group, borneol chemotype naphtha group, camphor chemotype naphtha group, isocamphane chemotype naphtha group and natural borneol group. Rats of the triptergium wilfordii control group were given orally 8.1 mg x kg(-1) triptergium wilfordii for 35 days, rats of the normal control group and model control group were given same volume water, and rats of other groups were given 80 mg x kg(-1) corresponding drug. We observed the rat common condition, weighed the rat body weight weekly, measured the degree of swelling of voix pedis every 4 days, weighed the thymus and spleen on the end of life, and measured the contents of cell factor TNF-alpha, IL-2, and IL-6 in rat blood serum. RESULT: As far as the arthrosis degree of swelling and the contents of cell factor TNF-alpha, IL-2, IL-6 were concerned, rats of model control group were higher than normal control group, and rats of other drug groups were lower than the model control group. The order of inhibition ratios of the arthrosis degree of swelling from high to low principle was isocamphane chemotype naphtha group, camphor chemotype naphtha group, borneol chemotype naphtha group and natural borneol group. All medication administration teams evidently reduced the contents of the IL-2 and IL-6, and the inhibition ratios were higher than 38%. In the case of the contents of TNF-alpha and IL-2, all groups were not evidently different. In the case of inhibition of IL-6, camphor chemotype naphtha group was better than borneol chemotype naphtha group and natural borneol group, the latter was better than isocamphane chemotype naphtha group. As far as the weight, thymus index and spleen index were concerned, all medication administration groups were not different. CONCLUSION: The different chemotypes of C. camphora have anti-inflammatory effect on the rat arthritis model induced by Freund's adjuvant, but pharmacological activity and mechanism of action are different. The study points out the clinical curative effects of the chemotypes of the kindred medicinal plant are different, and please consider the difference of chemotype in clinical application.

[Study on antiinflammatory effect of a compound TCM agent containing ant extractive in animal models].

OBJECTIVE: To study the antiinflammatory effect of a compound TCM (Traditional Chinese Medicine) agent on animal models. The agent contains ant extractive and a blent of three herbal products, herba epimedii, fructus cnidii, and fructus lycii. METHOD: Three animal models to induce experimental inflammation in rats, including carrageenin--induced paw edema, cotton-ball granuloma and adjuvant induced arthritis, were chosen to study the antiinflammatory effect of the TCM agent. RESULT: The TCM agent showed a marked inhibitory effect on edema induced by all three types of inflammation in rats, the inhibitory rate of the TCM agent at the dose of 0.20, 0.40 and 0.80 g.kg-1 in granuloma model bing over 25% at 1 hour post oral administration, and being 23.8%, 22.7%, 39.7% at 6 hour. In addition, the TCM agent also showed a significant preventive as well as therapeutic effect on adjuvant induced arthritis in rats, and improved the pathological changes of the animal joints with the induced arthritis. CONCLUSION: TCM agent has significant antiinflammatory effects on the three above mentioned animal models.