Researchers have discovered that natural compounds found in dark sweet cherries may reduce tumor growth, metastasis, and treatment resistance in triple-negative breast cancer. The study’s findings were published in the International Journal of Molecular Sciences.
The natural pigments that give dark sweet cherries their rich red color may also influence the growth and spread of an aggressive form of breast cancer. In a mouse study conducted at Texas A&M University, researchers found that these compounds were associated with slowed tumor growth, reduced metastasis, and changes in the activity of genes associated with treatment resistance.
The researchers focused on anthocyanins—plant pigments responsible for the color of fruits like dark cherries—and their impact on triple-negative breast cancer, for which there are relatively few treatment options and a high risk of spreading to other parts of the body. Researchers from Texas A&M University’s College of Agriculture and Life Sciences, Texas A&M AgriLife Research, and the College of Veterinary Medicine and Biomedical Sciences (VMBS) found that treatment with anthocyanins slows tumor growth, reduces cancer spread to multiple organs, and alters the activity of genes involved in metastasis and therapy resistance.
“Triple-negative breast cancer is considered the ‘worst’ because it is more aggressive, has a higher grade, and has a higher mitotic rate, meaning the cancer cells divide rapidly,” said Giuliana Noratto of the College of Agriculture and Life Sciences. “All of these characteristics increase the likelihood of spread to distant organs and recurrence compared to other types of breast cancer.”
Triple-negative breast cancer differs from other forms of the disease in that its cells lack estrogen receptors, progesterone receptors, and expression of HER2, a growth-promoting protein involved in regulating cell growth and proliferation. According to Noratto, without these molecular targets, treatment options are limited, and cancer is more likely to metastasize, particularly to the lungs and brain.
Instead of measuring only the size of primary tumors, the researchers also tracked metastatic spread, as metastasis is a leading cause of cancer-related mortality.
“This is important because cancer mortality is primarily due to metastasis,” Noratto said. “A large primary tumor that does not metastasize may be more manageable, and if removed, even curable.”
To determine whether anthocyanins could influence both processes, the researchers divided the mice into four groups. One group received no treatment, another received anthocyanins before tumor implantation, a third received the chemotherapy drug doxorubicin after tumor formation, and the fourth received both anthocyanins and chemotherapy.
This experimental setup allowed the researchers to study anthocyanins as a preventative measure and to test whether these compounds could improve the effectiveness of chemotherapy.
In mice given an anthocyanin-rich dark cherry extract before tumor implantation, tumors grew more slowly and showed no noticeable side effects. Furthermore, they continued to gain weight throughout the study.
In comparison, some mice given chemotherapy alone lost weight, and tumor growth slowed only later. In mice given both anthocyanins and chemotherapy, tumor growth slowed earlier, while body weight remained unchanged.
The researchers also analyzed gene expression within the tumors. Gene expression reveals which genes are “turned on” or “turned off,” which, according to Noratto, provides insight into the cellular processes affected by the anthocyanins in dark cherry. When used alone or in combination with chemotherapy, anthocyanins reduced the activity of genes associated with metastasis and therapy resistance—the process by which cancer cells adapt and continue to survive despite treatment.
Anthocyanin treatment also reduced the spread of cancer to the lungs compared to both untreated mice and mice receiving chemotherapy alone. Metastasis to the liver, heart, kidneys, and spleen was also reduced, although the number and size of tumors varied among individual animals.
More profound changes were detected in tumor tissue.
To connect these mechanisms,To examine the physical changes in cancer cells, Lauren Stranahan, a veterinary pathologist at VMBS, used histology—the microscopic examination of tissue samples.
Stranahan assessed the rate at which cancer cells divide—called the mitotic rate—as well as the extent to which metastatic cells had spread to various organs and whether this damage could impair organ function.
“Some tumors had higher mitotic activity, so they were dividing faster,” she said.
Some tumors also showed areas of necrosis, or tissue death, which can develop when a rapidly growing tumor cannot keep up with its existing blood supply.
Stranahan also studied the presence of immune cells in the tumors, including T cells, which help the immune system recognize and destroy abnormal cells, including cancer cells.
“By assessing the aggressiveness of a cancer, we can also evaluate whether the cancer is capable of reducing the number of T cells that attack it,” she said.
These findings also align with a broader trend in cancer research toward combining multiple approaches rather than relying on a single treatment.
“We now understand that no single cancer treatment will be effective against a specific disease,” Stranahan said. “Several different treatments will have to be used.”
Noratto noted that food-derived compounds could fit into this broader strategy by targeting cancer-related processes that standard treatments don’t fully address, providing researchers with additional biological pathways to explore.
Stranahan also emphasized the importance of integrating knowledge from various scientific fields when studying a disease as complex as cancer.
“The more people with different skills come together, the better you can evaluate a study from different angles, from unique perspectives, and the stronger the study will be,” Stranahan said.
She added that veterinary pathologists can contribute to many types of biomedical research, extending well beyond research focused solely on animal health.
“We do a lot of diagnostic work on patients here at the (Texas A&M University) Veterinary Teaching Hospital, but we can also provide significant research support,” Stranahan said.
These results are still preliminary, and further research will be needed to clarify how anthocyanins influence tumor behavior, including questions about their safety, absorption, and potential use alongside existing cancer treatments.
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