Modified natural compound inhibits blood vessel formation in neuroblastoma
Described in Scientific Reports, a study demonstrates that Dextran-Catechin, a modified natural compound, is able to suppress the formation of blood vessels in tumors by disrupting copper homeostasis.
Catechin, an antioxidant found in the leaves of the tea plant, is also present in certain foods like red wine, chocolate, berries, and apples. It has been known for a long time that catechin is beneficial to health. For this reason, many studies have been focused on it. Now we know that catechin has a moderate anti-tumor effect. But its poor stability in the body has limited its applications.
Recently, researchers from the University of New South Wales (UNSW) and collaborators found that catechin stability can be improved by the conjugation of catechin with dextran, referred to as Dextran-Catechin. Moreover, Dextran-Catechin shows a strong anti-tumor effect by affecting copper homeostasis in neuroblastoma.
Copper has an essential biological role, and copper homeostasis is tightly regulated by the body. The imbalance of copper homeostasis triggers a range of diseases. There is evidence that increased serum levels of copper are associated with the progression of cancer.
In the current study, the team further explored the effects of Dextran-Catechin. Working with human microvascular endothelial cells (HMEC-1), they found that Dextran-Catechin inhibited the formation of blood vessels, or angiogenesis. This indicates that Dextran-Catechin has antiangiogenic activity.
Angiogenesis plays a key role in the growth and spread of cancer. Tumors induce angiogenesis by secreting chemical signals. The newly formed blood vessels support tumor growth and metastasis by providing oxygen and nutrients. So inhibiting angiogenesis represents a way to combat cancer.
Furthermore, the team identified the mechanisms by which Dextran-Catechin inhibits angiogenesis. Dextran-Catechin induced the production of reactive oxygen species (ROS) and dysregulated the levels of the proteins that control copper transport, including CTR-1 and ATOX-1. As a result, copper homeostasis was disrupted. When the researchers knocked out ATOX-1 in HMEC-1 cells, they observed a significant reduction in angiogenesis. This indicates that the antiangiogenic activity of Dextran-Catechin is based on its ability to disrupt copper homeostasis.
Finally, The team tested Dextran-Catechin in in vivo models of neuroblastoma and found that the compound showed anti-angiogenic activity in vivo.
Collectively, the study suggests that compounds like Dextran-Catechin may combat cancer by inhibiting angiogenesis.
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