Targeted therapies, such as agents that inhibit angiogenesis, offer hope as complementary agents in cancer therapy. Angiogenesis-inhibiting agents have the potential for inhibiting tumor growth and limiting the dissemination of metastasis, thus keeping cancers in a static growth state for prolonged periods. Black raspberry (Rubus occidentalis) extract was discovered to be antiangiogenic (0.1% w/v) in a novel human tissue-based in vitro fibrin clot angiogenesis assay. Assay-guided fractionation of a crude black raspberry extract resulted in a highly potent antiangiogenic fraction that accounted for only 1% of the fresh weight of whole black raspberries. At 0.075% (w/v), the active fraction completely inhibited angiogenic initiation and angiogenic vessel growth. Further subfractionation of this active fraction revealed the coexistence of multiple antiangiogenic compounds, one of which has been identified as gallic acid. However, the individual subfractions did not outperform the active whole fraction. These findings suggest that an active black raspberry fraction may be a promising complementary cancer therapy. It is natural and potent enough for manageable dosing regimens. These extracts contain multiple active ingredients that may be additive or synergistic in their antiangiogenic effects. These observations warrant further investigations in animals and human trials.

noni, the juice of the fruit from the Morinda citrifolia plant, has been used for centuries as a medicinal agent. We tested the effects of noni juice in a three-dimensional fibrin clot matrix model using human placental vein and human breast tumor explants as sources for angiogenic vessel development. Noni in concentrations of 5% (vol/vol) or greater was highly effective in inhibiting the initiation of new vessel sprouts from placental vein explants, compared with initiation in control explants in media supplemented with an equivalent amount of saline. These concentrations of noni were also effective in reducing the growth rate and proliferation of newly developing capillary sprouts. When used at a concentration of 10% in growth media, noni was able to induce vessel degeneration and apoptosis in wells with established capillary networks within a few days of its application. We also found that 10% noni juice in media was an effective inhibitor of capillary initiation in explants from human breast tumors. In tumor explants which did show capillary sprouting, the vessels rapidly degenerated (2-3 days) in those exposed to media supplemented with 10% noni.

Bone morphogenetic proteins (BMPs) have multiple biologic functions, including bone formation and embryonic induction. One of these proteins, BMP-6, was reportedly expressed at high levels in human prostate cancers that had also metastasized to bone. This study investigated both BMP-6 mRNA and protein expression in normal and malignant rat and human prostate tissues. BMP-6 was detected in both rat normal prostate and in Dunning rat-prostate adenocarcinoma sublines. The levels of BMP-6 mRNA and protein were similar for normal and malignant rat prostate, regardless of the metastatic potential. Moreover, castration had no apparent effect on BMP-6 production in rat normal ventral prostate, suggesting an androgen-independent gene regulation of this protein. BMP-6 mRNA and protein were also produced by normal and neoplastic human prostate cancer (radical prostatectomy specimens and human carcinoma cell lines DU145 and PC3). BMP-6 mRNA and protein expression, however, was higher in prostate cancer as compared with adjacent normal prostate, with higher-grade tumors (Gleason score of 6 or more) having greater BMP-6 immunostaining than the lower-grade tumors (Gleason score of 4 or less). Taken together, these results suggest that BMP-6 protein expression may serve as a potential marker for prostate cancer but not as a metastatic marker. Moreover, BMP-6 may contribute to prostate neoplastic behavior even in the absence of androgens.