Scientists from the National Medicines Institute and the University of Warsaw have discovered that the simultaneous administration of two organic substances used in cancer therapies results in the tumour shrinking faster with fewer negative effects of the drugs on healthy cells. A different synergistic effect was also observed – the tissues of the malignant tumour had a higher concentration of the substance that destroys the cell, and that these substances take longer to degrade by cell enzymes.
Two scientists discovered this: dr hab. Katarzyna Wiktorska, Professor of the National Medicines Institute, and dr hab. Maciej Mazur, Professor at the Faculty of Chemistry of the University of Warsaw. This is the result of extensive research and experimentation that the National Medicines Institute and UW have been jointly conducting for 10 years.
Promising synergism – an almost-two-fold better response of the malignant tumour
The discovery is related to the synergy of actions of doxorubicin and sulforaphane. Doxorubicin is an antibiotic widely used in anti-cancer therapies. Sulforaphane is a plant-derived substance found mainly in cruciferous plants (brassicas) and their sprouts, including Brussels sprouts, cabbage, broccoli, cauliflower, kohlrabi, kale, turnips and radishes. The scientists discovered that the simultaneous administration of both of these substances results in an almost two-fold better reduction in the size of the tumour compared with each substance being administered in isolation.
The studies were carried out under in vitro conditions – using tumour tissues and healthy tissue, and under in vivo conditions – in mice implanted with one of the most malignant breast cancers – triple-negative breast cancer – for which there is currently no fully effective treatment.
The key factor in the research was the use of nanotechnologies – doxorubicin and sulforaphane were administered in an aqueous solution in liposomes, i.e. two-layer phospholipid vesicles. “As we know, tumour tissues have a slightly different blood vessel structure compared with healthy tissues. Rapidly multiplying cancer cells need a lot of nutrients – the blood vessels surrounding them tend to be porous, and their walls are more permeable. Therefore, by using the right liposome size, we can selectively target cancer cells with higher amounts of medication while limiting the medications reaching healthy cells, where the blood vessels find it difficult to let through liposomes of this size. In our studies, we wanted to evaluate the extent to which the therapy we are working on can be targeted and act specifically on cancer cells. Our results to date look extremely promising,” explained Katarzyna Wiktorska, Professor of the National Medicines Institute.
Administering both substances using liposomes results in greater accumulation of doxorubicin in the cells. Sulforaphane makes the cell-killing antibiotic remain in cellular structures for longer – studies conducted previously by the team show that sulforaphane inhibits enzymes that degrade doxorubicin particles in the tumour’s cells. Thanks to this, these cells die quicker. “What’s most interesting, however, is that the use of liposomes results in doxorubicin not being as toxic in healthy cells as it is in cancer cells. This is a very important discovery that shows that in the future, chemotherapy based on doxorubicin doesn’t have to be as toxic and destructive to the entire body, and that it can be much more effective at killing cancer cells,” said Professor Maciej Mazur of the Faculty of Chemistry.
“This project is sufficiently advanced that it requires significant funding from an external entity that in the future will have an impact on the use of the research results in actual therapies. The acquisition of such a partner will allow us to go through all further stages required, from testing toxicity and confirming optimal concentrations of both medications to obtain the best results, to clinical trial phases. We are aware that although current studies look promising, the road ahead to implement this novel therapy may take several years,” said dr Robert Dwiliński, director of the Technology Transfer Centre of the University of Warsaw.