PSP002

In this study, the antiproliferative activity of peanut skin procyanidins (PSP) and six fractions (PSP-1∼6) isolated from PSP by several chromatographic steps on the human prostate cancer DU145 cells were evaluated. The results showed that PSP and PSP-1∼6 significantly inhibited the proliferation of DU145 cells. PSP-2 was the most effective fraction, which was identified as procyanidin B₃ mainly and procyanidin dimer [(E)C-luteolin or keampferol] secondarily. Moreover, the mechanism of antiproliferative activity of PSP-2 was investigated. It was observed that PSP-2 induced apoptotic cell death and cell cycle arrest at S phase in DU145 cells. PSP-2 caused the increase of intracellular ROS level and the decrease of Bcl-2/Bax ratio, and triggered the activation of p53 and caspases-3 in DU145 cells. Our findings demonstrated that procyanidins from peanut skin have the potential to be developed as an anti-prostate cancer agent.

Copper is an essential trace metal that has been implicated in angiogenesis, the formation of new blood vessels. As tumor growth relies on establishing a functional capillary network for blood supply, copper chelation therapy may hold promise as an anti-cancer strategy by suppressing angiogenesis. To test the anti-angiogenic effect of PSP-2, a recently developed high affinity Cu(I) chelator with low zeptomolar dissociation constant, we utilized the endothelial cancer cell line EAhy926 and assessed changes in cell migration, proliferation, and tube formation in Matrigel. In addition, sprouting was assessed by the chicken and sheep aortic ring assay, and vascular pattern formation was studied in the chorioallantoic membrane of chicken embryos (CAM assay). While incubation with PSP-2 resulted in selective depletion of cellular copper levels, cell migration was not affected and the proliferating activity was even slightly increased. Moreover, the endothelial tube formation assay revealed significant morphological changes in the presence of PSP-2, with thicker tubular walls and an overall decreased meshes area. Similarly, the aortic ring assay and CAM assay showed that PSP-2 evokes significantly longer sprouts with smaller angles at branching points. Altogether, PSP-2 exhibits significant bioactivity at concentrations as low as 5 μM, rendering it a promising anti-angiogenic agent. As EAhy926 cells exhibit both endothelial and tumorigenic properties, the anti-angiogenic effect of PSP-2 might potentially translate also into anti-cancer activity.