The Antitumor Activity Of Albaconol And Its Effect On DNA Topoisomerase Activity And Angiogenesis Activity In Vitro

To study the antitumor activity of Albaconol from Albatrellus confluens, the effect on DNA topoisomerase (TOPO) and angiogenesis activity in vitro. METHODSrThe cytotoxicity of Albaconol on human leukemia K562 , breast carcinoma Bcap-37, gastric adenocarcinoma BGC-823 and lung adenocarcinoma A549 cell lines were determined by MTT assay and the results were expressed as IC50 values; The inhibitory effect of Albaconol on tumor growth was observed by the models of implanted sarcoma 180 (SI80) and hepatoma 22 (H22) in mice and the results were expressed as inhibitory rate of tumor growth; The effect of Albaconol on DNA topoisomerase activity was measured by agarose gel electrophoresis using Plasmid pBR322 DNA as the substrate; The antiangiogenesis activity of Albaconol on human microvascular endothelial cells (HMECs) was investigated by HMECs growth inhibition assay ( MTT assay ) , Wounding Migration Assay and Matrigel Tube Formation Assay. RESULTS:The results showed that the IC50 values of Albaconol on K562, Bcap-37 > BGC-823 and A549 cell lines were 2.42+1.77, 1.8811.4K 1.0410.64 and 1.1811.10 ng/ml, respectively; The inhibitory rates of tumor growth at doses of 0.87, 1.74, 3.48 mg/kg of Albaconol on S180 and H22were 28.2 %, 43.2 %, 47.4 % and 15.6 %, 22.4 %, 37.8 %, respectively; Albaconol influenced obviously the activity of DNA TOPO II, stimulated DNA cleavage and inhibited DNA reunion mediated by TOPO II; Albaconol inhibited the proliferation of HMECs, the IC50 values were 17.52?.13 g/ml. Furthermore, Albaconol strongly inhibited the migration ability of HMECs induced by hEGF in a dose-dependent manner and greatly inhibited capillary-like networks development of HMECs. CONCLUSION:Albaconol exhibited significant antitumor activity in vitro and in vivo;-3-Albaconol targeted specifically DNA TOPO II , which is one of the mechanisms of its antitumor action: Albaconol has strong angiogenic effect on three important sequential angiogenic cascades and antiangiogenesis is one of the mechanisms of its antitumor action.