Anti-angiogenic activity of the flavonoid precursor 4-hydroxychalcone.

Angiogenesis, the growth of new blood vessels, is necessary for cancerous tumors to keep growing and spreading. Suppression of abnormal angiogenesis may provide therapeutic strategies for the treatment of angiogenesis-dependent disorders. In the present study, we describe the in vitro and in vivo anti-angiogenic activities of the flavonoid precursor 4-hydroxychalcone (Q797). This chalcone (22μg/ml) suppressed several steps of angiogenesis, including endothelial cell proliferation, migration and tube formation without showing any signs of cytotoxicity. Moreover, we found a selective effect on activated endothelial cells, in particular with resting endothelial cells and the human epithelial tumor cell lines (HeLa, MCF-7, A549). In addition, Q797 was able to modulate both vascular endothelial growth factor (VEGF)- and basic fibroblast growth factor (FGF)- induced phosphorylation of extracellular signal-regulated kinase (ERK)-1/-2 and Akt kinase. It did not influence the nuclear translocation of p65 subunit of the nuclear factor-κB (NF-κB) when human endothelial cells were stimulated with tumor necrosis factor (TNF)-α. Taken together this indicates that the Q797-mediated inhibition of in vitro angiogenic features of endothelial cells is most likely caused by suppression of growth factor pathways. The potent inhibitory effect of Q797 on bFGF-driven neovascularization was also demonstrated in vivo using the chick chorioallantoic membrane (CAM) assay. In summary, this chalcone could serve as a new leading structure in the discovery of new potent synthetic angiogenesis inhibitors

Targeting tumor-associated macrophages by anti-tumor Chinese materia medica

Tumor-associated macrophages (TAMs) play a key role in all stages of tumorigenesis and tumor progression. TAMs secrete different kinds of cytokines, chemokines, and enzymes to affect the progression, metastasis, and resistance to therapy depending on their state of reprogramming. Therapeutic benefit in targeting TAMs suggests that macrophages are attractive targets for cancer treatment. Chinese materia medica (CMM) is an important approach for treating cancer in China and in the Asian region. According to the theory of Chinese medicine (CM) and its practice, some prescriptions of CM regulate the body's internal environment possibly including the remodeling the tumor microenvironment (TME). Here we briefly summarize the pivotal effects of TAMs in shaping the TME and promoting tumorigenesis, invasion, metastasis and immunosuppression. Furthermore, we illustrate the effects and mechanisms of CMM targeting TAMs in antitumor therapy. Finally, we reveal the CMM's dual-regulatory and multi-targeting functions on regulating TAMs, and hopefully, provide the theoretical basis for CMM clinical practice related to cancer therapy