Targeting Homocysteine and Hydrogen Sulfide Balance as Future Therapeutics in Cancer Treatment

Abstract

A high level of homocysteine (Hcy) is associated with oxidative/ER stress, apoptosis, and impairment of angiogenesis, whereas hydrogen sulfide (H2S) has been found to reverse this condition. Recent studies have shown that cancer cells need to produce a high level of endogenous H2S to maintain cell proliferation, growth, viability, and migration. However, any novel mechanism that targets this balance of Hcy and H2S production has yet to be discovered or exploited. Cells require homocysteine metabolism via the methionine cycle for nucleotide synthesis, methylation, and reductive metabolism, and this pathway supports the high proliferative rate of cancer cells. Although the methionine cycle favors cancer cells for their survival and growth, this metabolism produces a massive amount of toxic Hcy that somehow cancer cells handle very well. Recently, research showed specific pathways important for balancing the antioxidative defense through H2S production in cancer cells. This review discusses the relationship between Hcy metabolism and the antiapoptotic, antioxidative, anti-inflammatory, and angiogenic effects of H2S in different cancer types. It also summarizes the historical understanding of targeting antioxidative defense systems, angiogenesis, and other protective mechanisms of cancer cells and the role of H2S production in the genesis, progression, and metastasis of cancer. This review defines a nexus of diet and precision medicine in targeting the delicate antioxidative system of cancer and explores possible future therapeutics that could exploit the Hcy and H2S balance.

Supplementation of sperm cryopreservation media with H2S donors enhances sperm quality, reduces oxidative stress, and improves in vitro fertilization outcomes

“…While, in the mentioned studies, oxidative stress was induced by in vivo or in vitro ROS-generating systems, in the current study, we used freezing process as a model to induce oxidative stress damage in goat sperm. Hydrogen sulfide (H 2 S) possesses potent antioxidant properties and can effectively counteract superoxide anions 53 and scavenge other harmful reactive oxygen species (ROS), thereby mitigating oxidative stress and preserving cellular integrity. The sulfide similar to other small thiols such as cysteine and GSH may act as a redox-controlling molecule 54 , 55 .…”

Evolving CAR-T-Cell Therapy for Cancer Treatment: From Scientific Discovery to Cures

“…These modifications include targeting multiple targets, immune checkpoint blockade, etc. Many combination strategies with existing treatments were also applied, which showed promising results for improving the efficacy of CAR-T therapy in both solid and hematological malignancies [ 215 , 216 ]. Indeed, more research and advanced knowledge in CAR-T-cell therapy are necessary to treat solid tumors in the near future.…”

How the Western Diet Thwarts the Epigenetic Efforts of Gut Microbes in Ulcerative Colitis and Its Association with Colorectal Cancer

“…In DNA methylation, the methyl group comes from the methionine cycle [118,119]. During the methionine cycle, first the amino acid methionine (which comes from diet) is converted to S-adenosyl methionine (SAM), then different DNA methyltransferases (DNMTs) transfer the methyl group from SAM to cytosine residues of DNA, producing S-adenosyl homocysteine (SAH) [120,121]. In addition to methionine (an essential amino acid), metabolites such as folate, vitamin B12, betaine, and choline are essential for SAM production [122][123][124].…”