Grape seed extract blocks a protein that helps tumors get their blood supply, according to City of Hope researchers. The study, published in the April issue of the journal Carcinogenesis, also showed how the extract accomplishes the feat.

Researchers in City of Hope’s divisions of Tumor Cell Biology and Molecular Medicine found that grape seed extract blocks the production of vascular endothelial growth factor, or VEGF.

Wei Wen, right, and co-author Jianming Lu are examining how grape seed extract might help starve tumors. (Photo by Darrin S. Joy)

VEGF is a protein that stimulates the growth of new blood vessels, a process called angiogenesis. VEGF often is extremely active in tumors, which need blood vessels to bring them nourishment to maintain their rapid growth.

Wei Wen, Ph.D., assistant professor of molecular medicine and senior author on the study, devotes much of her research to screening compounds for VEGF-blocking abilities.

“I’m particularly interested in natural products that can block angiogenesis,” she said.

Compounds that block angiogenesis have proven effective against cancers such as colorectal and kidney tumors.

Grape seed extract is a popular dietary supplement. Previous research has shown the extract can slow or prevent the growth of certain tumors, and recent studies suggest it can block blood vessel growth.

Wen said she learned about the potential of grape seed extract through studies by Shiuan Chen, Ph.D., professor and director of the Division of Tumor Cell Biology. Chen’s studies have shown the extract blocks another protein that helps promote some breast cancers.

Wen obtained grape seed extract from Shen and found it could block production of VEGF.

She and her team then sought to understand exactly how it worked. They found grape seed extract actually lowers the level of another protein that cells need to make VEGF. That protein, called hypoxia-inducible factor 1α, or HIF-1α, becomes more active when oxygen levels are low, such as when oxygen-rich blood is in short supply.

When oxygen is scarce, HIF-1α bumps up VEGF levels to make more blood vessels. In tumors, this process is amplified to feed the cancer’s ravenous need for oxygen and other nutrients carried by blood.

Blocking HIF-1α, and in turn VEGF, would choke off the tumor’s blood supply, starving it.

In a study published last year in Cancer Prevention Research, the researchers also found that grape seed extract can block VEGF signaling through another mechanism as well, potentially making the extract doubly potent.

The researchers hope to build on their findings and eventually study grape seed extract’s anticancer effects in combination with other therapies.