c. with K562 cells into the right flank. The K562 bearing mice were randomly divided into four groups and treated with vehicle and Jac A at a dose of 2, 10, or 50 mg/kg daily for 21 days. As selleck chemical Enzastaurin shown in Figure 6A C, Jac A dose dependently inhibited tumor growth. Higher doses of Jac A had a better inhibitory effect and longer observed survival time. Interestingly, the body weight of the con trol group and mice treated with the low dose of Jac A were significantly lower than mice from higher dose groups. This phenomenon can be attributed to the low toxicity and therapeutic effect of Jac A. In the process of this ex periment, the tumors growths of mice from higher dose groups were significantly inhibited and the quality of life better than control group and low dose group.

The absorbed energy from food mainly used for keep ing the growth of tumor for mice in control group and low dose group, which contribute to losing weight. However, this phenomenon improved in higher dose groups. This finding suggests that Jac A can effectively inhibit the growth of tumor in vivo with low toxicity. Discussion Many anti cancer drugs have significant side effects, and some cancers are drug resistant. There fore, potential anti cancer compounds are needed in pharmaceutical development. Natural products, with inherently larger scale structural diversity than syn thetic compounds, are the major resources of bioactive agents and will continue to provide the most candi dates for new drug discovery. Many natural product resources have been used as medicine, such as those in traditional Chinese medicine.

Active compounds from medicinal plants are generally biologically friendly, because of their clinical use. Here, we identified a new natural Bcl 2 inhibitor Jac A with potential therapeutic use in murine models of human leukaemia via high throughput screening of our in house NPL and bio logical testing. Jac A, a characteristic constituent of H. japonicum, was firstly reported by Kyoko Ishiguro et al. and charac terized by its inhibitory effect on PAF induced hypotension. In this work, Jac A was identified as a new inhibitor of Bcl 2 proteins. We found that Cilengitide Jac A can compete for binding to BH3 domain of Bcl 2 proteins with proapoptosis proteins in the FP based binding experiments. This result was confirmed by the co immunoprecipitation experiment whose results showed Jac A can inhibit the heterodimerization be tween antiapoptotic proteins with pro apoptotic proteins in K562 cells. Moreover, Jac A showed potent activity in indu cing the apoptosis of K562 cells. Simultaneously, we found that Jac A can promote the release of cyto chrome c into cytosol and trigger the activation of downstream protein containing caspase 9, caspase 3, and PARP.