A natural compound isolated from onions is able to reduce the progression of ovarian cancer by interfering with the myeloid cells found in the tumor microenvironment, a new study published in Scientific Reports found.
The study, “Onionin A inhibits ovarian cancer progression by suppressing cancer cell proliferation and the protumour function of macrophages,” conducted at Kumamoto University in Japan suggests that this compound, called onionin A (ONA), may have the power to enhance existing anti-cancer agents with little additional toxicity.
Epithelial ovarian cancer is one of the most lethal female cancers worldwide. Although it is ranked 10th among female cancers, it is the fifth cause of cancer death among women in the United States.
Because nearly 80 percent of patients relapse following their initial treatment with chemotherapy, new and more effective lines of treatment are required to improve the outcomes of epithelial ovarian cancer patients.
Tumor-associated macrophages are key components of the ovarian cancer microenvironment, and are thought to be involved in the dissemination of cancer cells into the peritoneum.
Macrophages can differentiate into various activation states depending on the chemical signals found in their microenvironment. In ovarian cancer, nearly all tumor-associated macrophages differentiate into an M2 state, which is known to promote tumor growth, generation of new blood vessels, metastasis formation, and immunosuppression.
Therefore, macrophage polarization into an M2 stage and their interaction with tumor cells have emerged as possible targets to halt epithelial ovarian cancer progression.
In a previous study, the Kumamoto University research team attempted to identify natural compounds that could inhibit this macrophage differentiation, and found that the onion compound ONA could prevent this differentiation.
Now, the researchers found that this happens because ONA interferes with the function of STAT3, a transcription factor (proteins that regulate gene expression) involved in M2 polarization and cancer cell proliferation. Consistently, ONA not only inhibited the generation of pro-tumor macrophages, it also significantly inhibited cancer cell proliferation.
Also, the team found that ONA could inhibit another type of myeloid cells found in the tumors, called myeloid-derived suppressor cells (MDSCs). These cells are known to exert immunosuppressive functions, impairing the tumor-killing T-cells from effectively recognizing and killing the cancer cells.
To determine whether ONA could be used to enhance the anti-tumor effects of preexisting drugs, the researchers tested the compound in combination with Taxol (paclitaxel), Paraplatin (carboplatin), and Platinol (cisplatin).
ONA was found to enhance the effect of all these drugs both in culture and in ovarian cancer animal models. Mice treated with both chemotherapy and ONA had longer lifespans and halted tumor development without visible cytotoxic effects. The researchers believe this effect was mainly derived from ONA’s effect on the M2 macrophages.
“ONA is an orally available small molecule that may be an effective adjuvant therapy for patients with advanced epithelial ovarian cancer,” the researchers wrote.