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Chitosan — A Means to Combat Cancer?

Por: | 30 de septiembre de 2013

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By Jan Ignacak, Jagiellonian University in Krakow

Cancer treatment is among the major challenges of contemporary medicine. New studies raise hopes for an ultimate selection of a substance that — while inhibiting cancer cell metabolism — will not affect the metabolism of normal cells. Possibly, such compound might be chitosan — a product of chitin depolimerisation and deacetylation.

The process of neoplasm development — carcinogenesis or oncogenesis — is a multistage process that consists of an accumulation of genetic changes, usually occurring over many years, which lead to a loss of control over cell division and differentiation. These cells are referred to as “undergoing neoplastic transformation”. Further changes, which may take place as a consequence of mutations occurring in the genetic code, may lead to a neoplasm becoming malignant, i.e., acquiring the ability to metastasize.

Interest in the biochemical peculiarities of cancers dates back to the 1930s. The first reports demonstrating the accelerated metabolism of glucose under aerobic conditions were published by Otto Wartburg. (Glucose is a basic substrate for energy generation in each cell.) Papers by Pasteur indicated glycolysis inhibition under aerobic conditions in normal cells and the lack of such an effect, or its limitation, in cancer cells. Additionally, Crabtree showed that an increased glucose concentration resulted in diminished oxygen consumption in cancer cells. The milestone in the studies on glucose metabolism in cancer cells was the observation addressing enzymes that regulate the glycolysis rate.

Cancer treatment is among the major challenges of contemporary medicine. In spite of employing the most modern diagnostic, therapeutic and preventive techniques, no selectively acting pharmaceutical has been developed to date that can contribute to arresting or obliterating a neoplastic process without having a negative effect on normal cells at the same time. Contemporary medicine has at its disposal many therapeutic methods that are used in combating neoplastic disease. Some of them are quite effective, while others are successful to a lesser degree. But all these methods provide an opportunity for curing the disease, especially in the initial stage of the neoplastic process. Prevention plays an important role in protecting individuals against the disease. Prevention of malignancies includes all activities that reduce the risk of cancer morbidity, since it is much easier to prevent the disease from developing than to treat it later. Nevertheless, the elementary, but important, problem continues to be identification of the carcinogenic factors and understanding the mechanisms of their action. This knowledge would, at a later stage, allow high-risk groups that may develop malignant disease to be defined.

Interdisciplinary studies carried out jointly with the Chair of Medical Biochemistry, Jagiellonian University Medical College, Krakow and the Institute of Biopolymers and Chemical Fibres, Lodz, raise hopes for an ultimate selection of a substance that — while inhibiting cancer cell metabolism — will not affect the metabolism of normal cells. Possibly, such compound might be chitosan — a product of chitin depolimerisation and deacetylation. Chitin is predominantly found in the shells of crustaceans — shrimps and crabs — and in the tissues of fungi and bacterial cell walls.

In addition to cellulose, lignin and proteins, chitosan is a natural polymer that is biodegradable. As chitosan is non-toxic for animal organism it is being increasingly employed as a carrier of various medications and nucleic acids as well as proteins.

The polymer has been proved to inhibit the glycolytic activity of cancer cells. This activity is triggered by, among other factors, an increased synthesis of the enzymes involved in the process of glycolysis. These enzymes include those that regulate the rate of the process, which shows a variable sensitivity to the effectors influencing its activity, as compared to corresponding enzymes in normal cells. Inhibition of the glycolytic activity of cancer cells is directly associated with their decreased energy generation: this energy being necessary for the intense synthesis of both nucleic acids and proteins, substances indispensable for the prompt division of these cells.

A chitosan molecule, because of its size, does not have the ability to penetrate into the cell. The constructional unit of the polymer is a glucose molecule. This glucose molecule has an amine group (-NH2) in place of the hydroxyl group (-OH) at the second carbon atom. It is this amine group that contributes to the polymer molecule acquiring a positive charge. The polymer cation interacts with the negatively charged membrane of the neoplastic cells. This interaction contributes to inhibiting their growth, decreasing membrane permeability for various substances and decreasing the metastasizing potential of the cancer cells. No such effects are observed in the interactions between chitosan and normal cell membranes.

Studies concentrating on the products of chitosan degradation point to even better inhibitory effects on both glycolytic activity and the rate of cancer cell division. These positively charged molecules are supposed to exhibit a higher ability to interact with the negatively charged surface of the cell membrane. In addition, they are most likely capable of penetrating through the membrane into the cells.

The main objective of the present studies is to select the most effective molecules capable of selectively inhibiting the metabolism and division of cancer cells and their ability to metastasize.


Jan Ignacak
Jagiellonian University in Krakow

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