One of Soria Natural's strategic objectives is the development of scientific studies to discover and support the pharmacological properties of plants and the products generated from them.
His latest research project, Determination of the antitumor properties of CTP in combination with vitamin C in human cancer carrying the KRAS mutation, was carried out in collaboration with the Jiménez Díaz Foundation, through the Center for the Development of Industrial Technology (CDTI), of the Ministry of Science and Innovation, co-financed by the European Regional Development Fund (ERDF), and lasted three years.
Soria Natural has among its catalog of natural products, a food supplement called CTP, a cellular detoxifier that is marketed in tablets. Soria Natural has a patent for this product, made from the plant Lepidium latifolium. This product was brought to market after years of research in collaboration with the University of Salamanca and the Cancer Research Center; in that work, published in the prestigious journal Molecular Carcinogenesis in March 2018, it was observed that the active principle of the plant had an important antitumor action on different tissues.
For its part, the Fundación Jiménez Díaz has been studying for years the benefits of vitamin C in certain cancers carrying mutations in the KRAS gene, which are resistant to conventional therapies. Specifically, the Translational Oncology Department, led by Dr. Oscar Aguilera, has focused on the study of the effect of vitamin C on the glycolytic metabolism of tumor cells. Compared with the corresponding healthy tissues, pancreatic and colorectal tumors of patients carrying a mutation in the KRAS gene exhibit a special avidity for the use of glucose as an energy source and show a very high expression of the transporters of this metabolite, as well as of other molecules associated with the maintenance of Warburg metabolism.
Both entities therefore decided to pool knowledge and technology to tackle this new project, in which the aim was to shed light on the properties of the two products (CTP and vitamin C) alone or in combination, on the anti-inflammatory and proapoptotic effects and the molecular mechanisms
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underlying this anti-tumor action. The cell lines under study have a mutation in the KRAS gene, which confers them a high resistance to both chemotherapy and biological therapies directed at the target, and are two lines of human colorectal cancer (SW480 and DLD-1) and two lines of pancreatic adenocarcinoma (PL-45 and MIA PaCa-2).
The results show that all four lines are sensitive to both compounds and that there is a dose-dependent proapoptotic effect, i.e. the greater the amount of compound, the greater the effect observed. Likewise, a cytostatic effect has been achieved, whereby a substance allows blocking cells in a certain phase of the cell cycle, thus preventing their replication.
On the other hand, assays carried out with macrophages (healthy cells of the immune system) showed that both compounds are able to inhibit the inflammation peaks generated after uncontrolled induction of proinflammatory cytokines with a bacterial lipopolysaccharide.
The FJD has analyzed which genes, cell signaling pathways and metabolic processes are regulated by these two molecules. The results reveal that both substances are capable of drastically altering the mitochondrial membrane potential, affecting energy production (ATP); both vitamin C and CTP have drastically reduced the expression of the proto-oncogene C-myc, inferring that both molecules are interfering with the proliferative processes of the tumor cell. CTP clearly possesses c-Myc inhibitory activity, whereas the activity of vitamin C seems to be rather mediated by interference with enzymes involved in cellular energy production processes.
These results support the hypothesis that both factors act on different signaling pathways, although with a similar result: dramatic inhibition of tumor cell growth. The combination of both compounds seems a promising option to prevent inflammatory processes, so involved in the onset of cancer and degenerative diseases, and to sensitize solid tumors to therapies commonly used in the clinical management of cancer. This is a surprising finding, since until now, there has been no effective therapy to control the growth of tumors carrying mutations in the KRAS gene. Pharmaceutical designs targeting this molecule have not yielded relevant data in terms of patient survival or improvement in quality of life.
The results of this research are relevant and promising, so the next step is to consider future in vivo trials, including the possibility of conducting a clinical trial in humans.