Asbestos research20.02.2020

A synthetic plant hormone as a new strategy for the treatment of malignant tumours

Mesothelioma are tumours, which are mainly caused by the inhalation of asbestos fibres, and are as yet incurable. However, there is a molecule, which has a strong inhibiting effect on the growth of these tumours. It is normally used as a growth hormone in the agricultural production of fruit. Two research teams of the University of Fribourg are now providing new insights on the effect of this molecule, forchlorfenuron (FCF).

Conventional methods of treating mesothelioma patients comprise chemotherapy, radiation therapy and surgery to remove the tumour, often in combination. To date, none of these treatments has led to striking success. One reason for this is that cancer cells subjected to long-term chemotherapy develop resistance to cancer medication.

Inhibition of tumour cells by a plant hormone
A completely new approach is now being tested by two Fribourg research teams led by Prof. Beat Schwaller, Department of Medicine, and Prof. Christian Bochet, Department of Chemistry. Earlier experiments had shown that the protein calretinin can interact with the protein septin 7 in mesothelioma cells. They now set about investigating the effect of a direct repression of the septin function(s) in mesothelioma cells. Such an inhibitor exists in the form of forchlorfenuron (FCF), which is ranked as relatively harmless to human health. This substance is used in agriculture (mainly in the USA and China) as a plant hormone and increases the rate of growth of fruit.

Prof. Schwaller’s group has now shown that FCF strongly inhibits the growth – i.e. the cell cycle of mesothelioma cells – in cell cultures in vitro. Interestingly, the growth of tumours in other tissues (lung, colon, prostate, ovary, breast) is also strongly inhibited by FCF.

An alternative to conventional cancer medication
Pilot experiments carried out in vivo in mice indicate that blocking the function of septins might represent a new approach for the treatment of mesothelioma. Since little is known about the molecular mechanism of action, Prof. Schwaller’s researcher group joined with the team of Prof. Christian Bochet, Department of Chemistry. The chemists then synthesised and characterised a series of FCF-analogous substances, which were subsequently tested in mesothelioma cells in relation to their effect on cell growth. They found that the chlorine atom of FCF is absolutely essential for septin binding and the resultant biological effects.

Further investigations are in progress to possibly discover new molecules, which are even more effective than FCF. The two research teams are convinced that the research on septin inhibitors should be continued, since they represent an alternative approach to conventional cancer medication. The future will tell, whether septin inhibitors will make it to clinical research or even will be considered for therapeutical applications.

A real problem despite prohibition
Mesothelioma develops from the mesothelial cells, which line our body cavities like wall panels. When asbestos fibres are inhaled, small needle-shaped mineral fibres enter the body and eventually mesothelial cells, which may lead to the formation of malignant mesothelioma, mainly in the pleura. The human body is incapable of either breaking down or eliminating these fibres. Because mesothelioma only develops 20-40 years after exposure to asbestos, the number of patients in Switzerland, as well as elsewhere will continue to increase, even though the use of asbestos has been prohibited since 1990.

Further Information
Link to the scientific journal Oncotarget