The Aiti-tumor Effect Of Baicalein In Vivo

With a high morbidity rate in America and the euro area, prostate cancer havebeen a serious threat to the health status of middle aged and old men all the time. Inrecent years, the incidence of prostate cancer in China was gradually increasedwhich makes the drug development for prostate cancer, especially androgenindependent prostate cancer therapy more and more important. Proteasomeinhibitors, like bortezomib, as a new aspect of anticancer drugs, have achieved a bigsuccess in clinic through specifical inhibition of the proteasome activity whichconsequently induce suppression of tumor growth. But the existing proteasomeinhibitors have high cytotoxicity to normal tissue and show little effect on solidtumor, reminding us a underlying iceberg to be discovered.The nature compounds extrated from Chinese traditional herbal medicineusually show lower physiological toxicity compared with synthetic drugs. Themultiple structures and functions of nature compounds of Chinese medicine havealso attracted the researchers’ attention. For example, Celastrol is extacted fromThunder God Vine which can cause proteasome inhibition and induce tumor growthsupression revealed a new application of herbal medicine component in cancertherapy.We’ve found several potential proteasome inhibitors through computersimulation. Baicalein, noticed a kind of flavonoid with high scores in moleculardocking experiment was proved to be capable of inhibiting the CT-Like activity ofpurified20S proteasome. The results of cytology experiment showed that areversible binding between Baicalein and the active site of proteasome which causedthe accumulation of ubiquitinated proteins， and indicated other cell signalingpathways were also invoved in Baicalein induced cell death. It was worth noting thatBaicalein has poor stability in vitro and behaves differently in various cell lines. Onthe basis of cytological experiments, we established prostate cancer xenograft modelin nude mice to explore growth suppression effect of Baicalein on prostate cancer invivo. After28days treatment with20mg/Kg/day dosage, the mices maintainednormal body function which provided a safe durg concentration range ofBaicalein.But the growth suppression effect was not detected during the experiment.Mices treated for7days under the same dosage were sacrificed and no inhibition ofproteasome activity was found in tumor tissues. Moreover, the truth that cell deathinduced by other pathways were not detected in vivo demonstrated Baicaleintransformed quickly in vivo and caused the reduction of pharmacodynamic effects.Compeared with correlational studies, Baicalein reveals a limitation of application on xenograft of prostate cancer cell line PC-3. These results will provideexperimental evidences and theoretical basis for the improvement of Baicalein andits derivatives in the development of proteasome inhibitors.