Spices against cancer
Russian scientists have found a medical use for dill and parsley
Russian scientists from the Moscow Institute of Physics and Technology (MIPT) Institute of Organic Chemistry named after Zelinsky RAS, the N. K. Koltsov Institute of Developmental Biology of the Russian Academy of Sciences, and the Institute of Cell Biophysics of the Russian Academy of Sciences proposed an effective synthesis of substances with anticancer activity based on compounds isolated from parsley and dill seeds. The results of the study are published in the Journal of Natural Products (Semenov et al., Efficient Synthesis of Glaziovianin A Isoflavone Series from Dill and Parsley Extracts and Their in Vitro/in Vivo Antimitotic Activity).
"Today, an important task is not only to find new mechanisms to fight cancer, but also to improve existing ones. We have developed a simple way to obtain glaziovianin A and its structural analogues that inhibit the growth of tumor cells from cheap plant raw materials. In addition, our team has developed an in vivo ("inside the living") system on sea urchin embryos for fast and reliable determination of the mechanism of action of new anticancer drugs," says MIPT Professor Alexander Kiselyov.
No growth of cancer cells
Currently, chemotherapy is the main method of drug treatment of cancer. It is carried out by antimitotics – substances that suppress the growth of tumor cells due to disruption of their division process – mitosis. Cancer cells divide much more often than usual, and therefore suffer more from the action of antimitotics. So, in three days, the number of melanoma cells can increase by 2 times, while the number of their healthy precursors – melanocyte cells - even when division is stimulated increases by only 15%.
Microtubules consisting of the protein tubulin play an important role in mitosis. Antimitotics bind to tubulin (exhibit antitubulin activity) and destroy microtubules, which in turn leads to the inability of cells to complete division and eventually to death. In nature, such substances are found mainly in tropical plants.
The object of this work is a potent antimitotic substance glaziovianin A, contained in the leaves of the Brazilian tree Ateleia glazioviana Baill. The laboratory synthesis of such a substance is quite complex and requires expensive precursors (substances that participate in the reactions necessary to obtain the final product) and catalysts (accelerators of chemical reactions). The authors of the article proposed a new six–stage (conventional synthesis contains 9 stages) synthesis of glaziovianin A. Precursors for it were obtained from seeds of common plants - parsley and dill.
The scheme for obtaining glaziovianin A (from an article in the Journal of Natural Products).
In addition to glaziovianin A, a number of its structural analogues were also synthesized to search for new promising substances-antimitotics. Antitumor activity was tested in two ways: on sea urchin embryos and on human cancer cells.
On sea urchins and cancer cells
Sea urchin embryos were used as a tumor model because their cells actively divide in the early stages of development. The test substance was added to the aqueous medium with the embryos and concentrations were determined, leading to a change in the fission rate and its complete stop. The lower these concentrations, the greater the antimitotic activity of the substance. When division is disrupted due to specific antitubulin activity, sea urchin embryos, as the authors previously established, begin to rotate, this interesting effect can be observed in a conventional light microscope. Using embryos, it is possible to determine not only the antimitotic effect, but also the general toxicity of the drug to cells, its specificity to the tumor, as well as the effectiveness of its penetration through the cell membrane – these are important parameters for further study of anticancer drugs in higher animals.
To confirm the antitumor effect, the synthesized compounds were tested not only on model animals (sea urchins), but also on various human cancer cells: lung carcinoma cells; melanoma; prostate, breast, colon and ovarian cancers. Healthy blood cells were taken as a control. Experiments have shown that the substances studied most effectively limit the growth of melanoma cells, and have practically no detrimental effect on healthy blood cells.
Among the studied substances, according to the authors, two analogues of glaziovianin are promising for use in medicine as medicines. However , the best indicators of antitumor activity out of 12 compounds were shown by glaziovianin A.
Since the synthesized substances have shown efficacy on human cancer cells and model animals, the authors plan to further test them on experimental oncological models (human tumors inoculated with laboratory mice).
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04.07.2016