May 15th 2025:
CÚRAM researchers have developed a way to more effectively target nitric oxide, or NO, which can be an important driver of some breast cancers. They focused on a chemical called hemin, which can grab onto NO. Hemin tends to clump together in watery environments, which limits its use in medicine, but by giving hemin a smart ‘chemical makeover’, the scientists have made it more suitable for use in the body.
Find out more in this short Q&A with CÚRAM and University of Galway post-doctoral researcher Dr Amir M. Alsharabasy, in conversation with Dr Claire O’Connell:
What role does Nitric Oxide play in enabling the spread of tumour cells in some breast cancers?
Nitric oxide (NO) is a small molecule naturally made by our bodies, but in certain aggressive breast cancers, like triple-negative breast cancer, too much NO can cause problems. High levels of NO help cancer cells move, invade nearby tissues and eventually spread (or metastasise) to other parts of the body. NO does this by affecting the cancer cells’ ability to change shape, move faster and break down barriers that usually keep tissues intact.
How could controlling nitric oxide be useful for treating aggressive breast cancer?
By lowering or “scavenging” the extra NO around the cancer cells, we can slow down or even stop their ability to move and spread. Instead of blocking the body’s natural production of NO completely – which could have harmful side effects – scavenging focuses on simply removing the excess NO that’s helping the tumour spread. This makes it a safer, more targeted way to treat aggressive breast cancers like triple-negative breast cancer.
What is Hemin, and how does it control NO? And what’s the problem with using Hemin as a treatment in the body?
Hemin is a naturally occurring molecule made of iron and a special ring-shaped structure. It’s similar to the part of haemoglobin that carries oxygen in our blood, which we call heme. Hemin can “catch” and neutralise NO by binding to it tightly, making it a great natural scavenger. However, there’s a problem: when hemin is added to water-based solutions, its molecules tend to stick together and form clumps. This is a process called aggregation. When hemin clumps, it becomes less effective at capturing NO and can also break down more easily, limiting its use as a medicine.
How have CÚRAM researchers figured out a way to stop Hemin from clumping while retaining its ability to control NO in the body?
Our lab, which is led by Professor Abhay Pandit at CÚRAM, came up with a smart but simple chemical strategy. We attached small molecules – tyrosine and tyramine, which are related to natural amino acids – to hemin. This simple “chemical makeover” stopped the hemin molecules from clumping together. By doing this, we kept hemin’s ability to trap NO but made it much more stable in the body’s watery environment. We also found that these modified hemin molecules could still easily enter cancer cells and reduce NO levels inside them, preventing cancer cell movement without being quickly destroyed. We carried out the work with colleagues in Spain and Germany.
What could the impact of this research be for more effective breast cancer treatments in the future?
These findings could lead to new, safer treatments that stop aggressive breast cancers from spreading by targeting a major enabler, excess nitric oxide, without harming normal body processes. Because the modified hemin is more stable and effective, it could be used on its own or alongside other treatments like chemotherapy or radiotherapy to improve patient outcomes. In the future, it could form part of a new class of anti-metastatic drugs designed to stop breast cancer from coming back or spreading after surgery.
You can read the full paper in Small Science here: Facile Synthesis of Hemin Derivatives with Modulated Aggregation Behaviour and Enhanced Nitric-Oxide Scavenging Properties as New Therapeutics for Breast Cancer
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