Hydroethanolic root extract of Croton membranaceus suppresses angiogenesis in zinc–testosterone-induced prostate adenocarcinoma and chorioallantoic membrane models

Angiogenesis plays a pivotal role in the growth, progression, and metastatic spread of cancer cells. However, the clinical utility of current antiangiogenic agents has been limited by the emergence of drug resistance, thereby highlighting the need for novel therapeutic candidates, including natural products. Croton membranaceus has previously been shown to suppress prostate cancer cell growth and may represent a potential antiangiogenic agent. In this study, we investigated the effect of Croton membranaceus hydroethanolic root extract (CMERE) on new blood vessel formation. The zinc-testosterone-induced prostate adenocarcinoma model was used to assess microvessel density and the effect of 10, 30 and 100 mg/kg of CMERE on relative expressions of platelet-derived growth factor receptor beta (Pdgfrβ). Vascular length, diameter, density and other vascular indices were assessed in the chick chorioallantoic membrane (CAM) assay following single treatment with either normal saline, enzalutamide (1 µM) or CMERE (10, 30–100 µg/ml). We could show that CMERE reduced microvessel density and suppressed the expression of Pdgfrβ in the rat prostate. CMERE also significantly reduced vessel density, length and diameter, and also disrupted the normal vascular tree structure, decreasing the number of junctions and microcirculatory routes in the CAM. These findings demonstrate that CMERE effectively inhibits angiogenesis, supporting its potential as a source of antiangiogenic agents for treatment of diseases with aberrant angiogenesis such as prostate cancer.