Prospects of molecular hydrogen in cancer prevention and treatment.

Abstract

Gaseous signaling molecules such as carbon monoxide, nitric oxide, and hydrogen sulfide have established precedents for gas-based oncological applications. Hydrogen gas (H₂), a mildly reductive molecule, has emerged as a candidate in this field. Evidence indicates that H₂ selectively neutralizes highly reactive oxygen species (ROS) and suppresses ROS-dependent intracellular signaling, thereby reducing cancer cell proliferation and metastatic potential. In the context of radiation and chemotherapy, H₂ appears to attenuate oxidative tissue damage and immunosuppression, with potential implications for prognosis. Immunologically, H₂ has been associated with inhibition of T cell exhaustion and enhancement of anti-tumor T cell activity. Notably, the human gut microbiota constitutes a continuous endogenous source of H₂, which may contribute to systemic tumor resistance. This review consolidates current understanding of gut-flora-derived H₂ and immune homeostasis, the mechanistic basis of H₂'s anti-tumor activity, and practical delivery considerations, aiming to inform future research directions in comprehensive cancer care.

Mechanism

H₂ selectively scavenges highly cytotoxic ROS such as hydroxyl radicals and peroxynitrite, suppressing ROS-dependent signaling pathways that drive cancer cell proliferation and metastasis; this ROS-neutralizing capacity is also proposed to underlie H₂'s immunomodulatory effects, including inhibition of T cell exhaustion and enhancement of anti-tumor immune responses.