Antioxidants in antidiabetic drugs may fuel cancer spread, mouse study shows

Researchers working in mice with cancer now find that some of these drugs can spur the metastasis of existing tumors, including colon and liver cancer. If borne out in humans, the findings caution against giving this type of antioxidant-containing medication to diabetic cancer patients.

Mounting evidence from animal studies highlights the potential of antioxidants, compounds that protect cells from toxic reactive oxygen species, to accelerate either cancer growth or metastasis. Antioxidants are commonly used to treat patients with diabetes, a disease driven by oxidative stress.

Diabetes is suspected to raise the risk of many cancers, and the number of diabetic patients who also have cancer is growing. However, how antidiabetic drugs affect cancer is poorly understood.

Hui Wang and colleagues studied the effects of two common classes of antidiabetic medications with antioxidant properties in mice with colon and liver cancer. They found that while these drugs did not raise the risk of developing cancer, they sped the metastasis of existing tumors. Antioxidants in the drugs seemed to protect cancer cells from oxidative stress, boosting their ability to migrate and invade.

Cell experiments revealed that the drugs activated the NRF2 signaling pathway, which triggered the expression of metastasis-promoting proteins. Indeed, deleting or blocking NRF2 markedly reduced cancer cell migration. Analysis of liver tumor samples from patients showed that NRF2 expression correlated with tumor metastasis.

In light of these results, the researchers call for further studies evaluating the safety of antioxidant-containing medications for diabetic patients with cancer. Their finding in mice would need to be confirmed in humans before researchers would make any definitive clinical recommendations.