The last project, Determination of the antitumor properties of the product CTP in combination with Vitamin C in KRAS mutations in human cancer (CTPC), which has lasted three years, was carried out in collaboration with the Jiménez Díaz Foundation and received support from the Center of Development of Industrial Technology (CDTI) of the Ministry of Science and Innovation, co-financed by the European Regional Development Fund (ERDF).
The catalog of natural products of Soria Natural includes a food supplement called CTP, a cellular detoxifier in tablets. Soria Natural has a patent for this product, made from the plan Lepidium latifolium, which was launched on the market after years of research in collaboration with the University of Salamanca and the Cancer Research Center. In this project, published in the renowned journal Molecular Carcinogenesis in March 2018, it was observed that the active principle of this plant had an important antitumor action on different tissues.
The Jiménez Díaz Foundation has been studying for years 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 Oscar Aguilera (MD), 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.
Thus, both entities decided to join knowledge and technology to develop this new project, in which the objective was to explore the properties of the two products (CTP and vitamin C) alone or in combination, their anti-inflammatory and proapoptotic effects, and the molecular mechanisms underlying their antitumor 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).
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 observed, whereby a substance allows cells to be blocked at a certain stage of the cell cycle, preventing their replication.
In addition, tests carried out with macrophages (healthy cells of the immune system) showed that both compounds are able to inhibit the inflammatory peaks generated after uncontrolled induction of proinflammatory cytokines with a bacterial lipopolysaccharide.
The Jiménez Díaz Foundation has also analyzed which genes, cell signaling pathways and metabolic processes are regulated by these two molecules. The results show 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 c-myc proto-oncogene, suggesting 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 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 effect: dramatic inhibition of tumor cell growth. The combination of both compounds seems to be a promising option to both prevent inflammatory processes 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 with KRAS gene mutations. Pharmaceutical studies focused on this molecule have not shown relevant data in terms of patient survival or improvement in their quality of life.
The results of this research are relevant and promising. Therefore, the next step will be to consider in vivo studies or even a clinical trial in humans.
