Vitamin E Succinate May Control Tumor Growth and Boost Immunotherapy

Recent research from the University of Chicago Medicine highlights the potential of vitamin E succinate (VES) as an effective agent in combating tumor growth and enhancing the efficacy of immunotherapy. This study, published in the Proceedings of the National Academy of Sciences, reveals how VES promotes the degradation of fat mass and obesity-associated protein (FTO), which has been linked to increased tumor proliferation and resistance to immunotherapeutic treatments.

FTO is a known demethylase involved in epigenetic regulation, specifically in the removal of methyl groups from RNA. The presence of these methyl groups typically stabilizes RNA, promoting healthy cellular functions. However, FTO's activity can lead to reduced RNA stability, contributing to tumor development. The research team, led by Professor Yu-Ying He, focused on identifying substances that could effectively degrade FTO, which has been found to be upregulated in various forms of cancer.

Previous studies indicated elevated FTO levels in melanoma, a type of skin cancer, influenced by environmental factors like UV radiation and arsenic exposure. Despite the identification of several small molecule inhibitors for FTO, their clinical application has been limited due to toxicity concerns. In this context, the researchers turned to vitamin E succinate, a well-known dietary supplement with an established safety profile.

Through molecular docking techniques, the study confirmed that VES binds effectively to FTO, facilitating its degradation. The researchers established that DTX2, an E3 ubiquitin ligase, plays a critical role in this process. VES operates by simultaneously binding to both FTO and DTX2, enhancing the degradation of FTO and functioning as a molecular linker.

To further examine how VES impacts tumor progression and enhances immune responses, the research team conducted a series of experiments. The findings indicated that VES significantly boosts T-cell mediated cytotoxicity, thereby suppressing tumor growth through FTO inhibition. The implications of these results suggest that VES could serve as a promising therapeutic strategy for cancers characterized by high FTO levels and resistance to conventional immunotherapy.

This study represents a significant advancement in cancer treatment, particularly for cases where traditional immunotherapy has been ineffective. The researchers emphasize the potential of VES in transforming cancer therapy, especially in overcoming challenges associated with FTO-related tumor resistance.