Anti-cancer Constituents Research Of The Higher Polar Substances From Desmodium Caudatum (Thunb.) DC

Cancer prevalence is rising fast in the world. Malignant tumor has become the second primary human "killer" just following cardiovascular diseases in the past decades. Traditional Chinese medicine has several thousand years of clinical research experience, making great contributions to preventing and treating diseases. Because of the advantages including less toxic side effects, diversified structure, abundant production, extracting effective anti-cancer ingredients from natural products has became one of the most significant approaches in anticancer research. In this project, on the basis of previous research on the weak polar substances isolated from Desmodium caudatum (Thunb.) DC. in our group, the chemical constituents and antitumor bioactivity of the higher polar substances from Desmodium caudatum (Thunb.) DC. were investigated.In our study,29compounds were isolated from the60%ethanol extract of Desmodium caudatum (Thunb.) DC. by using the methods of silica column chromatography, polyamide column chromatography, ODS column chromatography, Sephadex LH-20chromatography, thin layer chromatography (TLC), recrystallization, analytical HPLC, preparative HPLC, etc. The structures of these compounds were identified on the basis of the data from NMR, MS spectra, physical properties and chemical properties. Among the29compounds, there are12flavonoids,6phenylpropanoids,2steroids,3stilbenes,2alkaloids and4other types of compounds. Compounds4,5,10,11,12,16,17,20,21,24,25,26,27,28,29were separated from Desmodium genus for the first time.Compound15and Compound19are two new compounds and both of them have the chemical structure segment of β-D-apiofuranosyl-(1â†'6)-β-D-glucopyranoside.All the compounds were evaluated by MTT assay to detect the antitumor activity. The results showed that compounds13,27could inhibit the growth of cancer cell HeLa significantly, and they exhibited good concentration dependence at the same time. Compounds13,27were verified long-range killing function to the growth of HeLa by the clonogenic assay. PARP cleavage of compounds13,27were examined for further studies in HeLa cells. The results showed that all of the two compounds could promote PARP cutting and exhibited good concentration dependence also. Compounds13,27could increase the activities of caspase-3, caspase-8and caspase-9. In addition,2compounds were screened through dual luciferase report gene test. Compound13could drastically enhance the transcription of nuclear receptor RXRa, and also promot the transcription of RXRa while cooperating with9-cis-RA. All results suggested that compound13induced apoptosis and inhabited the growth of human cancer cells may through the activation pathway of RXRa.