Chronic stress and the consequent release of the stress hormone epinephrine may help breast cancer cells grow by helping them get more energy, a study in mice shows. This effect might be reversed through treatment with vitamin C, researchers report.
The researchers first wanted to examine how stress affects tumor development. To do this, they stressed mice by confining them in a small habitat for a month. The stressed mice exhibited behaviors that resembled anxiety and depression, suggesting that the model was effective at generating mouse stress.
The mice were then injected with mouse or human cancer cells. Tumors in the stressed mice grew faster and got larger than tumors in mice that hadn’t been stressed.
The researchers found that breast cancer stem cells were particularly enriched in the tumors of stressed mice. These cells are thought to drive most of the problematic aspects of cancer, such as tumor spread and the development of drug resistance.
“You can kill all the cells you want in a tumor, but if the stem cells, or mother cells, are not killed, then the tumor is going to grow and metastasize. This is one of the first studies to link chronic stress specifically with the growth of breast cancer stem cells,” Keith Kelley, PhD, a professor at the University of Illinois and an author of the study, said in a press release.
Further investigation revealed that the stressed mice had especially high levels of the hormone epinephrine. The researchers tried treating stressed mice with a drug that blocks the epinephrine receptor — a protein called ADRB2 — and found that tumors in these mice grew less. This supported the idea that epinephrine was helping drive the cancer cells’ growth.
The researchers figured out that, when epinephrine binds to ADRB2 on cancer cells, it causes the cells to make more of a protein called lactate dehydrogenase. Normally, this protein works to metabolize sugars, which helps give cells like muscle cells quick bursts of energy so they can do work. However, in cancer cells, this protein helps the cells make energy they need to divide out of control, driving tumor progression.
When the investigators examined samples from 83 breast cancer patients, they found that those with higher levels of epinephrine had more lactate dehydrogenase in their tumors. These patients also had lower survival rates than their low-epinephrine counterparts.
Finally, the researchers tested a variety of drugs on cancer cells to see whether they could interfere with this cancer-promoting system. They found that a few compounds, including vitamin C, could decrease the cancer cells’ production of lactate dehydrogenase. When they injected mouse tumors with vitamin C, the tumors shrank.
“Taken together, these findings show that vitamin C might be a novel and effective therapeutic agent for targeting cancer in patients undergoing chronic stress,” said Quentin Liu, PhD, of Dalian Medical University, another of the study authors.
Further tests and clinical trials will be needed to determine to what extent these findings are applicable to humans and, if they are, to figure out how best to use them to treat breast cancer.
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