Microscopic view of cancer cells intertwined with hydrogen sulfide pathways, symbolizing hope for future cancer therapies.

Can Hydrogen Sulfide Hold the Key to Cancer Treatment?

Rhea Morgan in Health & Wellness December 2025 • 4 min read.

"Unlocking the Potential of 3-MST in Cancer Therapy: A Deep Dive into New Research"

Hydrogen sulfide (H2S) is now recognized as a key biological messenger in our bodies, similar to nitric oxide and carbon monoxide. Produced by several enzyme systems, H2S plays diverse roles in health and disease. Recent studies indicate that cancer cells boost their H2S production, using it to fuel their growth, energy, and blood vessel formation. This fascinating area of research is opening new doors in cancer therapy.

Initially, scientists thought cystathionine-beta-synthase (CBS) was the main source of H2S in tumors. Later, cystathionine-gamma-lyase (CSE) was also found to be significant. Now, there's growing interest in 3-mercaptopyruvate sulfurtransferase (3-MST), another enzyme that produces H2S. Its unique properties, like its location in mitochondria and its ability to create polysulfides, make it a strong candidate for influencing cancer.

This article delves into the potential of 3-MST and H2S in cancer, highlighting recent findings that suggest 3-MST plays a key role in cancer cell survival, bioenergetics, and signaling. We will also address the questions that remain and outline potential research strategies.

What is 3-MST and How Does It Produce H2S?

Microscopic view of cancer cells intertwined with hydrogen sulfide pathways, symbolizing hope for future cancer therapies.

3-MST, a protein known for decades, functions as a 33 kDa, zinc-dependent enzyme. It exists in monomer-dimer form, and its monomer is the active form. Crucially, Cys154 and Cys263 are involved in intermolecular disulfide formation, which affects the enzyme's activity (Fig. 1). This enzyme is found in both the cell's cytoplasm and mitochondria.

The intracellular distribution can be related to two splice variants of the enzyme. Both of these variants (TUM1-Iso1 and TUM1-Iso2) have similar enzymatic activity, but different localization: TUM1-Iso1 is cytosolic, while TUM1-Iso2 exists both in the cytosol and in mitochondria [20]. 3-MST appears to be present in all mammalian tissues, although its expression levels are tissue-dependent; kidney, liver, brain, testes, large intestine and endocrine organs show especially high expression levels [18].

Antioxidant and Detoxification: Early research highlighted 3-MST as an intracellular antioxidant and detoxification enzyme.
tRNA Thiolation: 3-MST is involved in modifying cytosolic tRNAs, known as TUM1 (tRNA thiouridin modification protein 1).
Polysulfide Production: 3-MST can produce polysulfides, as demonstrated by Hylin and Wood in 1959.

The production of H2S requires the combined action of 3-MST and cysteine aminotransferase (CAT). The sulfur from 3-mercaptopyruvate is transferred to Cys247 in 3-MST's active site. This persulfide then releases H2S with the help of intracellular reductants like thioredoxin or dihydrolipoic acid.

The Future of 3-MST Research

The 3-MST/H2S system in cancer cells is complex and influenced by cell type and context. Future research should focus on its role in mitochondrial function, proliferative signaling, and interactions within the tumor microenvironment. With new inhibitors and silencing techniques, scientists can explore how 3-MST affects tumor growth and drug resistance in animal models, potentially leading to new cancer therapies.

About this Article -

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Everything You Need To Know

What is the role of Hydrogen Sulfide (H2S) in cancer cells, and why is it significant?

Hydrogen Sulfide (H2S) is a key biological messenger that cancer cells utilize to promote their survival and growth. Cancer cells increase H2S production to fuel their bioenergetics, support blood vessel formation, and enhance their overall survival. This increased H2S production is significant because it provides cancer cells with a survival advantage, making H2S a potential target for cancer therapies. The research highlights that understanding and manipulating H2S pathways, specifically those involving enzymes like 3-mercaptopyruvate sulfurtransferase (3-MST), could revolutionize cancer treatment.

How does 3-mercaptopyruvate sulfurtransferase (3-MST) produce Hydrogen Sulfide (H2S), and what is its function?

3-MST, a zinc-dependent enzyme, produces H2S in conjunction with cysteine aminotransferase (CAT). The process involves the transfer of sulfur from 3-mercaptopyruvate to Cys247 in 3-MST's active site, creating a persulfide. This persulfide then releases H2S with the help of intracellular reductants like thioredoxin or dihydrolipoic acid. Besides H2S production, 3-MST also acts as an antioxidant and detoxification enzyme, is involved in tRNA modification (TUM1), and can produce polysulfides. The location of 3-MST in both the cytoplasm and mitochondria suggests diverse roles in cellular processes related to cancer.

Where is 3-MST located within the cell, and how does its location impact its function in cancer?

3-MST can be found in both the cytoplasm and mitochondria, which is related to two splice variants (TUM1-Iso1 and TUM1-Iso2). TUM1-Iso1 is located in the cytosol, while TUM1-Iso2 exists in both the cytosol and mitochondria. The dual location of 3-MST suggests that it can affect cancer cells in various ways. The mitochondrial presence highlights a connection to cellular bioenergetics and mitochondrial function, while cytosolic activity may influence signaling pathways. This dual localization underscores the potential for 3-MST to have a significant impact on cancer cell survival, proliferation, and response to therapies.

What are the key properties of 3-MST that make it a potential target for cancer therapy?

3-MST possesses several key properties that make it an attractive target for cancer therapy. It's located in both the mitochondria and cytoplasm, indicating multiple potential roles in cancer cell biology. Its enzymatic activity produces H2S, which fuels cancer cell growth. 3-MST also has the ability to produce polysulfides, adding complexity to its biological functions. Furthermore, research suggests that 3-MST plays a key role in cancer cell survival, bioenergetics, and signaling. These factors collectively make 3-MST a prime target for strategies aimed at disrupting cancer cell processes and improving treatment outcomes.

What are the future research directions for 3-MST in cancer therapy?

Future research should focus on several areas to fully understand the role of 3-MST in cancer. This includes investigating its influence on mitochondrial function, its involvement in proliferative signaling pathways, and how it interacts with the tumor microenvironment. Researchers plan to use new inhibitors and silencing techniques to study how 3-MST affects tumor growth and drug resistance in animal models. The goal is to develop new cancer therapies that target 3-MST, potentially by manipulating H2S production or inhibiting its activity. Further studies on the specific roles of different 3-MST variants are also needed to fully realize its therapeutic potential.