Anti-angiogenic and antitumor activities of Huaier aqueous extract

Traditional Chinese medicine, a rich source of potent cancer chemopreventiveagents, is attracting increasing attention worldwide. Recently, the anticanceractivity of Trametes robiniophila Μurr. (Huaier) has been widely investigated.However, the mechanisms are not yet fully understood. This study aimed to elucidatethe inhibitory effect of Huaier extract on angiogenesis and tumor growth. Incubationwith Huaier extract inhibited the proliferation of human umbilical vein endothelialcells (HUVECs) and mouse mammary tumor cells (4T1). In addition, treatment withHuaier extract decreased the motility and tube formation of HUVECs in a dose-dependentmanner in vitro. As determined by western blot analysis, Huaier extract dose-dependentlydecreased the levels of phosphorylated extracellular signal-regulated kinase (ERK),transcription factor p65, c-Jun N-terminal kinase (JNK), signal transducer andactivator of transcription 3 (STAT3) and the expression of vascular endothelialgrowth factor (VEGF). In ex vivo experiments, new vessel growth was suppressedas shown by chick embryo chorioallantoic membrane (CAM) and rat aortic ring assaysin the presence of Huaier extract. To further evaluate the inhibitory effect,4T1 cells were injected subcutaneously into BALB/c mice. The administration ofHuaier extract suppressed tumor volume, decreased microvessel density and inducedapoptosis. These data suggest that Huaier extract may serve as a potent anti-angiogenicand antitumor agent.