Dr. Andrew Quest: "from Curcumin we got a formulation that has very good bioavailability and biological activity to stop the metastasis in melanoma"
How to fight cancer? A question that science has been developing over decades through various lines of research. Indeed, such a complex disease has become a real challenge for thousands of scientists around the world, who many times with advanced technology testing different mechanisms to achieve objectives such as the stagnation of the metastatic process.
In Chile, various institutions and centers have research lines linked to cancer, and one of the largest reference is the center of advanced chronic diseases (ACCDiS). This unit, which emerged thanks to funding from the National Commission for scientific research and technology (CONICYT) and its program FONDAP, has produced many finds of great importance in the way to stop cancer. From the early and early detection of biomarkers associated with gastric cancer, or formulations nanotechnological holding molecules of gold, ACCDiS - the day today-is a true reference of national scientific research.
Member of ACCDiS is Dr. Andrew Quest, who from his laboratory in the program of cell biology and Molecular of the Institute of Biomedical Sciences of the University of Chile, has carried out joint research with other leading scientists from the Center, as the Dres. Marcelo Kogan and Felipe Oyarzun)Faculty of chemical and pharmaceutical sciences, University of Chile). This teamwork enabled researchers producing a nanoemulsion of Curcumin that large scale stops the proliferation of as aggressive as melanoma cancer.
The discovery, made in phase of experimentation in animal models, has caused great commotion, not only for the effectiveness of the carcinogenic processes but also by the accessibility of the raw material with which was held: Curcumin, turmeric structural molecule.
Dr. Quest is biochemist of the Instituto Federal de technology of Switzerland, Zurich and a doctorate in natural sciences from the same House of studies. Within its lines of research is the study of signal transduction with an approach to the understanding of the role of caveolin-1 protein in tumorigenesis, and the role of the bacterium Helicobacter pylori in the genesis of gastric cancer. Dr. Quest is Director of the Center for molecular studies of cell (CEMC) and Principal investigator and Scientific Director (cancer area) of the ACCDiS, where, along with other researchers, studying the mechanisms leading to the development of cardiovascular diseases and cancer.
Do impressions produced them this finding, in which Curcumin acted as a key factor to stop melanoma metastatic processes in animal models?
The truth is that these findings have been surprising in terms of its effectiveness, since one would not a priori think that something derived from the curry may help stop the metastasis. In this regard, I would like to emphasize that through research centers such as ACCDiS, we could generate transdisciplinary research lines between various professionals, which has allowed us to, among other things, integrate diverse knowledge for a product like the nanoemulsion of Curcumin.
Areas such as basic sciences and nanotechnology - strongly understood by the Dres. Marcelo Kogan and Felipe Oyarzun - were fundamental to create opportunities for conversation and funding for "out of the box" ideas like these.
Can ACCDiS the basic knowledge is extrapolen towards areas of greatest social impact?
No doubt that it does. In ACCDiS, we can develop a more associative science where we bring together ideas from various lines of research, more basic and more applied, in order to finally put them into practice and to generate products that may impact society, as it is the case of this nanoemulsion of Curcumin.
Why is Curcumin an important actor in this research?
Curcumin is known many years ago, thousands of years to be more specific. It was known that it had beneficial effects on human health. In the India and China, for example, used much as food in condiments, but also for alternative medicine, in that sense, many testimonies showed that it had beneficial effects on the human being.
In that sense, we are interested in taking advantage of this resource for the generation of a drug, since it has an ancient history that guarantees its effectiveness. On the other hand, with raw materials such as Curcumin - if we succeed to show the positive effect that generates scientifically - it is much easier to reach a phase clinical with human patients, since it is proven because his culinary background. The problem that has Curcumin is that it is very volatile and poorly soluble in water, what does not have very good bioavailability in the body.
In technical terms, what is Curcumin?
Curcumin is an organic molecule of large structure, hydrophobic and insoluble in water. People consume Curcumin in form of curry (multiple seasoning mixture), but does not take advantage of the active agent (Curcumin), well now that when a come it does virtually nothing to the system, perhaps it has effects on the intestine, but the greater part of the molecule will be destroyed in the stomach (very acid medium) or will be long because it is not dissolved.
How did the search to solubilize Curcumin?
The first great task was to find a way to solubilize the molecule, since although this could be achieved by using organic solvents such as ethanol (C)2H5OH) or dimethyl sulfoxide (CH₃SOCH₃), these could not be injected into humans in large doses, due to its high toxicity. So, that was not the solution. While many of the experiments that are found in the literature are made in this way, on the one hand, you manage to improve bioavailability, but on the other hand, you decrease the amount that you can inject because the solvent is harmful.
In that sense, we solve these problems designing this nanoemulsion of Curcumin.
What is the nanoemulsion of Curcumin?
The nanoemulsion of Curcumin is a preparation of liposomes (which have no adverse effect on the body) to which is added the Curcumin dissolved in an organic solvent. Subsequently mix and spontaneously, liposome encapsulated to Curcumin, then the solvent will be diluting progressively to disappear and leave many small liposomes with Curcumin inside. As to the outside of the liposome the medium is hydrophilic and inward hydrophobic, have Curcumin solubilized in a way compatible with the body.
What you followed then?
After generating the soluble Curcumin formulation, what we did was to show that these protein are not toxic to moderately normal cells, with whom we work in the laboratory, but if had toxic effects on Melanoma (of the type B16F10). By it not affected adversely to good cells but if bad (phase in vitro).
To prove that this served in a treatment, had to undergo in animal models, to allow us to investigate how a tumor cells form a tumor and what processes are involved in metastasis. It was then that we inject melanomas in an animal model and we hope that an initial tumor, which had already grown after 10 or 12 days formed (is very fast). Then we remove the tumor, this makes it a person trained by a qualified surgeon, with which we develop the methodology. This professional extracts the tumor and then, in a phase of analysis, we observed if there are recurrent tumor growth in the original place and metastasis to the lung.
The two processes on the same animal can be evaluated with the experimental system we developed a few years ago. It was then where we add the nanoemulsion and estimate - based on experiments in cells - how much had to add. In response, we ensure that with emulsion not had healing problems. Let Act the nanoemulsion for a range of 14 to 15 days and after we analyze in incident tumor site, where we realized in the model not the nanoemulsion of Curcumin-treated, there was lot of metastasis, and tumor while in the model which had applied the product, there was no tumor or metastasis, and if there was, was much lower than in the untreated model range.
What is the next step in this research?
First of all, I think that it is relevant to highlight that we achieve a formulation that has very good bioavailability and biological activity.
The next step is to apply this nanoemulsion in humans, in fact we developed it for melanomas because it is a cancer usually accessible in the skin and the experimentation is more affordable. Although at the beginning we had fear occupy melanoma by its well-known aggressiveness, the fact that we have achieved this effect on this type of tumor shows signs of the nanoemulsion can be applied successfully in any other type of cancer.
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Journalist:Patricio Grunert Alarcón. ®
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