New molecule will neutralize cancer cells
Scientists from leading French research institutes, including CNRS, CEA, the Curie Institute and INSERM, together with specialists from Oxford University and the University of Melbourne identified a new molecule with antitumor and antimetastatic effects. Due to a previously unknown mechanism of action, this compound effectively affects cancer cells resistant to traditional chemotherapy drugs, blocking not only their division, but also mobility, thus preventing the formation of metastases.
The ability of malignant cells to acquire resistance to chemotherapeutic drugs significantly limits the effectiveness of traditional cancer treatment protocols. In addition, the main cause of death of cancer patients is the spread of metastases through the body – secondary tumor foci. The solution of these two problems is the main task of specialists engaged in the development of new approaches to antitumor therapy.
A group of biologists and chemists has spent almost 10 years screening potential anti-cancer agents using a high-throughput robotic screening platform. During this time, they analyzed about 30,000 molecules and only recently discovered a compound that meets their requirements in the chemical library of the Curie Institute.
Liminib (Liminib), or Pyr1, is an inhibitor of the enzyme LIM kinase. It controls the dynamics of the internal skeleton of cells, which is a system of fibers, including actin filaments and microtubules, providing the ability of cells to multiply and move. These two functions are actively used by cancer cells, which makes LIM kinase a promising target for antitumor therapy.
A is the structure of the Pyr1 molecule; B – liminib stabilizes the microtubules of HeLa cancer cells. All microtubules are marked in red, only stable ones are marked in green. Unlike control cells treated with dimethyl sulfoxide (upper images), in cells treated with liminib (lower images), almost all microtubules are stabilized. One division of the scale corresponds to 10 microns.
To date, liminib is the only known LIM kinase inhibitor with antitumor effect. It deprives cells of mobility and the ability to divide by disorganizing the actin cytoskeleton and stabilizing the microtubule network.
Laboratory experiments have demonstrated the toxicity of liminib for several cancer cell lines, including those resistant to various chemotherapy drugs. Moreover, the results of a pilot preclinical study on a mouse model demonstrated not only the effectiveness, but also good tolerability of the compound.
The researchers believe that in the foreseeable future, their results can be used as a basis for the development of alternative methods of treatment for patients who do not respond to traditional therapeutic approaches.
Article by R. Prudent et al. Pharmacological Inhibition of LIM Kinase Stabilizes Microtubules and Inhibits Neoplastic Growth is published in the journal Cancer Research.
Evgenia Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the Centre national de la recherche scientifique: A new molecule with anti-cancer and anti-metastatic properties.
12.09.2012