When Antioxidants Go Rogue: How Glutathione Helps Cancer Cells Survive and Spread

A New Discovery About Cancer Survival

A recent study published in Nature (covered by Medical Xpress, August 2025) has uncovered a surprising role for glutathione, one of the body’s most important antioxidants.

Researchers found that a mitochondrial transporter protein called SLC25A39 allows glutathione to enter the mitochondria of cancer cells, giving them the resilience they need to survive the stressful process of metastasis (spreading to other organs).

This is significant because metastasis, not the primary tumour, is what causes most cancer deaths. The study suggests that blocking this transporter could, in the future, become a therapeutic strategy to stop cancer in its tracks.

How Normal Cells Go Rogue

All cells, healthy or cancerous, share the same basic blueprint, our human genome. Genes like SLC25A39 are present in every cell, because they are needed for survival.

But cancer arises when normal cells begin to “go rogue.” Instead of following the rules, they exploit normal genes and proteins for their own survival. In other words:

• Normal cells use genes like SLC25A39 in balance.

• Cancer cells abuse or over-express these genes, bending them to their own advantage.

This hijacking of normal processes is what makes cancer so difficult: it doesn’t invent new tricks, it steals ours, to help them survive.

Glutathione: The Body’s Protector, and Cancer’s Ally

Glutathione (GSH) is often called the “master antioxidant.” We make it naturally, from amino acids (glutamine, cysteine, and glycine). In healthy cells, it protects against oxidative stress, toxins, and inflammation.

But here’s the paradox:

• Healthy cells need glutathione to survive.

• Cancer cells exploit glutathione to survive.

When glutathione enters the mitochondria of cancer cells (via the SLC25A39 “doorway”), it activates survival programs that help them resist stress and avoid destruction.

This is particularly critical during metastasis, when survival becomes very difficult.

Metastasis: The Alcatraz Escape Analogy

Imagine a prisoner escaping from Alcatraz:

• First, he must get out of the prison (the primary tumour).

• Then he must survive the freezing, dangerous swim across the bay (the bloodstream).

• Even if he makes it, he still must evade the police waiting for him on the shore (the hostile new organ environment).

Most cancer cells die during this journey. But the ones that succeed are the ones that have the best survival tools. For metastatic breast cancer cells, glutathione in their mitochondria is one of those tools. It allows them to adapt to low oxygen, high stress, and the foreign environment of new tissues.

The Therapeutic Angle: Targeting SLC25A39

Here’s the exciting part:

• The doorway protein SLC25A39 is crucial for importing glutathione into mitochondria.

• Cancer cells rely on it far more than normal cells.

• Blocking this transporter could stop cancer cells from surviving metastasis, without shutting down glutathione function everywhere else.

The challenge for scientists is to find a drug or molecule that blocks SLC25A39 selectively in cancer cells. Too much inhibition in healthy cells would disrupt normal antioxidant defences, so precision is key.

Practical Takeaways: Supporting Antioxidant Pathways Safely

While we wait for therapies targeting SLC25A39, there are safe and effective ways to support your body’s natural antioxidant balance without risking unwanted cancer cell support.

Focus on Recycling Glutathione (Not Flooding It)

• Alpha-lipoic acid (ALA) helps regenerate glutathione

• Selenium cofactor for glutathione peroxidase

• Riboflavin (B2) and Zinc support glutathione enzymes

• Vitamin C & E (moderate doses) assist in redox cycling

Food-Based NRF2 Activation

Mildly stimulate your body’s master antioxidant switch through diet:

• Cruciferous vegetables (broccoli, cauliflower, rocket, watercress)

• Green tea

• Curcumin (turmeric)

• Garlic, rosemary, ginger

(Stick to food-first approaches; avoid very high-dose extracts which may paradoxically help cancer cells.)

Support Mitochondrial Health

• CoQ10, magnesium, L-carnitine

• Adaptogens (rhodiola, ashwagandha) for stress resilience

Lifestyle Approaches

• Intermittent fasting or fasting-mimicking diets (promote autophagy)

• Exercise (HIIT or resistance training boosts natural antioxidant enzymes)

• Cold exposure & breathwork (mild hormetic stressors build resilience)

Use Caution With

• High-dose glutathione or NAC supplements

• Mega-dosing synthetic antioxidants

• Overuse of concentrated sulforaphane/NRF2 activators

Final Word

This new research highlights a fascinating paradox: the very antioxidants that protect our cells can also help cancer survive and spread. The key lies in balance, supporting our body’s natural defences without overstimulating them.

Future therapies may one day target SLC25A39, the mitochondrial “doorway” for glutathione, to stop metastasis in its tracks. In the meantime, we can use diet, lifestyle, and gentle supplementation to support healthy antioxidant function safely.

References

1. Medical Xpress. Mitochondrial antioxidant found to drive breast cancer metastasis. August 18, 2025. Link

2. Wang Y. et al. The mitochondrial carrier SLC25A39 is essential for glutathione import and iron-sulfur cluster biogenesis. Nature, 2021.

3. Luengo A. et al. Metabolic requirements of breast cancer metastasis revealed by spatial metabolomics. Nature, 2025.

4. Trachootham D. et al. Redox regulation of cell survival in cancer. Nature Reviews Drug Discovery, 2009.