DNA double helix turning into a key, symbolizing new cancer therapies.

Can the "Third Gasotransmitter" Unlock New Cancer Therapies?

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Lena Kashyap in Health & Wellness June 2025 • 4 min read.

"Unveiling the potential of 3-MST and hydrogen sulfide pathways in cancer research and treatment, addressing a critical gap in understanding how these biological systems affect cancer cell behavior."


Hydrogen sulfide (H2S) has moved from being considered a toxic gas to being recognized as a crucial biological messenger in our bodies. Alongside nitric oxide (NO) and carbon monoxide (CO), H2S is now known to regulate various cellular functions. Understanding how H2S works and how it’s produced in our cells is critical for developing new treatments for various diseases.

While scientists have primarily focused on two enzymes, cystathionine-γ-lyase (CSE) and cystathionine-β-synthase (CBS), as the main sources of H2S, a third enzyme, 3-mercaptopyruvate sulfurtransferase (3-MST), is gaining attention. Researchers are investigating its potential role in cancer, due to its unique characteristics, such as its location within cells and its ability to produce polysulfides, which can modify proteins.

This article explores the potential of 3-MST and H2S in cancer, highlighting how cancer cells use these molecules to support their growth and survival. It also identifies gaps in our current knowledge and suggests directions for future research.

Why 3-MST Matters in Cancer Research

DNA double helix turning into a key, symbolizing new cancer therapies.

3-MST has been recognized as a mammalian protein for decades. It exists as a 33 kDa enzyme that depends on zinc. The active form consists of a monomer-dimer equilibrium, with the 3-MST monomer being the active component. Two specific cysteines, Cys154 and Cys263, are key in forming intermolecular disulfide bonds, which directly impacts how well the enzyme functions.

What makes 3-MST particularly interesting is its presence in different parts of the cell, including both the cytoplasm and the mitochondria. This dual location is influenced by two versions of the enzyme created through alternative splicing. One version, TUM1-Iso1, is found in the cytoplasm, while TUM1-Iso2 is present in both the cytoplasm and mitochondria. While both versions perform similar enzymatic tasks, their different locations suggest they might have specialized roles.

  • Antioxidant and Detoxification: Early research highlighted 3-MST's role in protecting cells from damage by acting as an antioxidant and helping in detoxification processes.
  • tRNA Thiolation: 3-MST is also critical in modifying transfer RNAs (tRNAs), essential molecules involved in protein synthesis. In this context, 3-MST is referred to as TUM1 (tRNA thiouridin modification protein 1).
  • Production of H2S and Polysulfides: More recently, 3-MST has been recognized for its ability to produce hydrogen sulfide (H2S) and polysulfides. These molecules have significant biological activity, influencing various cellular processes.
For 3-MST to produce H2S, it requires the help of another enzyme called cysteine aminotransferase (CAT). Together, they facilitate the biological synthesis of H2S. This process involves transferring sulfur from 3-mercaptopyruvate to a cysteine in 3-MST's active site. The sulfur is then released as H2S with the help of other molecules like thioredoxin or dihydrolipoic acid.

Future Directions: Unlocking 3-MST's Full Potential

While it's clear that the 3-MST/H2S system plays a role in cancer, many questions remain. Future research needs to clarify how this system interacts with other elements in the cellular environment and how it affects cancer cell energetics, signaling, and survival. With the development of specific 3-MST inhibitors and advanced research tools, we are now better equipped to explore these questions and potentially develop new cancer therapies.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

Everything You Need To Know

1

What is 3-MST and why is it important?

3-Mercaptopyruvate sulfurtransferase (3-MST) is an enzyme that functions as an antioxidant, assists in detoxification, and modifies transfer RNAs (tRNAs). It is also recognized for its ability to produce hydrogen sulfide (H2S) and polysulfides. Its significance lies in its potential role in cancer biology, particularly in how it supports cancer cell growth and survival.

2

Why is hydrogen sulfide (H2S) considered important in the body?

Hydrogen sulfide (H2S) is important because it acts as a crucial biological messenger in the body, similar to nitric oxide (NO) and carbon monoxide (CO). It regulates various cellular functions. Understanding how H2S is produced and functions in cells is vital for developing new treatments for diseases, including cancer, where it influences cell proliferation, bioenergetics, and treatment resistance.

3

What other enzyme is required for 3-MST to produce H2S, and how does this process work?

3-MST requires cysteine aminotransferase (CAT) to produce H2S. Together, these enzymes facilitate the biological synthesis of H2S. This process involves transferring sulfur from 3-mercaptopyruvate to a cysteine in 3-MST's active site. The sulfur is then released as H2S with the help of other molecules like thioredoxin or dihydrolipoic acid. The levels of CAT affect H2S production.

4

How does the location of 3-MST in the cell affect its function?

3-MST exists in two versions due to alternative splicing: TUM1-Iso1, found in the cytoplasm, and TUM1-Iso2, present in both the cytoplasm and mitochondria. Both versions perform similar enzymatic tasks, but their different locations suggest they may have specialized roles within the cell. This dual location allows 3-MST to influence cellular processes in different compartments, which is particularly relevant in cancer where energy production and redox balance are critical.

5

What should future research focus on to unlock the full potential of 3-MST in cancer treatment?

Future research should focus on clarifying how the 3-MST/H2S system interacts with other components in the cellular environment and how it impacts cancer cell energetics, signaling, and survival. The development of specific 3-MST inhibitors and advanced research tools will be essential for exploring these questions and developing new cancer therapies. The interaction between 3-MST, H2S, and the cellular environment will provide insights into cancer cell behavior and potential therapeutic interventions.

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