COLORECTAL CANCERS AND ANTI-CARCINOGENIC PROPERTIES OF CURCUMIN

Curcumin has been used in the traditional Indian medicine for its anti-inflammatory and anti-carcinogenic properties for centuries. A number of researchers have carried out promising studies on curcumin to investigate whether it can be a good and reliable therapeutic substance for various cancer types including colorectal cancers. These studies have been done on cell cultures, experimental animals and humans. New and detailed studies show that anti-carcinogenic properties of curcumin are revealed with its effects on potential multiple molecular targets. One of these target formations is activated types of KB cells and the other is activator protein 1, which is [AP-1]. This doublet in protein structure is important transcription factors (genetic programme) in cells. These substances control and regulate cell reproduction, immune response of cells, cell differentiation and programmed (physiological) cell deaths (apoptosis), and as mentioned, they are within the target of curcumin. It is also revealed that curcumin positively effects and regulates a number of complex intracellular molecular activities such as cyclooxygenase-2, metallopeptidases 2 and 9, tumor necrosis factor (TNF) playing a role in carcinogenesis.

POTENTIAL EFFECT OF CURCUMIN ON CANCER

Carcinogenesis is a very complex process and chain of activities, and it takes place in three main phases, which are initiation, promotion and progression. These too closely related processes occur in the following order: transformation of a normal cell into a cancerous cell (initiated cell) – (initiation phase), transition into precursor cancerous cell – preneoplastic cell (promotion phase), and formation of cancerous cell – neoplastic cell (progression phase). Research shows that curcumin affects certain parts of these processes. Inflammatory cases in carcinogenesis have a role in all three phases. Cancer emerges in a period of time in which oxidative stress, caused by the deterioration of free radical and anti-oxidant balance in favor of free radicals, and chronic inflammation occurs together. Inflammation, as is the case in the initial phase of cancer, transmits the reproduction signals in transformed initial cells. Initiation of tumor by inflammation and following malign developments were investigated, and it was found that cytokines, angiogenic factors and metallopeptidases (mmp-9) released by leucocytes due to inflammation play a supportive role in cancerous vascularization, cancerous cell reproduction and intratissue and metastatic dispersions. These details show that inflammation plays a role in three phases of cancer. What proves this is the existence of activated NF KB (Nuclear Factor Kappa B) transcription factors acting as inflammation mediator in the cancerous tissue.

NF KB activated in the cancerous tissue continues its function of cell growth and development, which is one of the mentioned fundamental tasks, in the malign tissue; it also carries out this task by resisting to anti-carcinogenic drugs and radiotherapy. Therefore, NF KB has become an indisputable target in the treatment of cancer [27]. The important role of curcumin in cancer treatment comes from its inhibiting effects on NF KB. This activity occurs in intracellular molecular level in very complex ways.

Furthermore, cyclooxygenase enzyme (COX-2) is secreted in high levels in sporadic colon cancers and adenomas, and COX-2 acts as a catalyst in production of prostaglandin. Excessive production of this substance initiates inflammatory conditions and leads to inflammatory developments in the body which causes pains and carcinogenesis. COX-2 catalyst is intensively present in cancerous tissue and promotes the development of cancerous tissue. Therefore, celebrex (celecoxib), COX-2 specific suppressors, were administered as supplementary treatment; however problems were experienced due to serious side effects (digestive system bleedings, kidney damages). It is found that curcumin, without any toxicity and side effects, is a perfect alternative (COX-2) inhibitor for celecoxib, and that it has highly protective and therapeutic effects on colon cancer and familial polyposis [46, 47, 52].

Colon cancers’ being near the top among all cancer types, especially in western countries, attracts the attention of cancer researchers. Therefore, developing herbal and chemical protection and treatment methods and researching a number of important molecular and cellular pathways are dealt as a priority.

Curcumin, in herbal protection and treatment studies, remains in the forefront with its various effects, and it is observed in experiments on humans that it has a significant anti-carcinogenic effect and that doses up to 8000mg are tolerated well in the human body. Values of curcumin assessed in blood serum were investigated, curcumin was administered to patients in three groups 450, 1800 and 3600mg a day, and the assessable serum values were found in the group to whom 3600mg curcumin was administered daily. Although more detailed studies are required to find standardized values, protective and therapeutic effects in the assessed doses and results of colon cancer are thrilling and promising.

Curcumin is a product derived from the rhizomes of the plant whose Latin name is Curcuma Longa in India and its vicinity and commonly used in regional dishes as a type of spice. The use of Curcuma Longa for its pain and inflammation removing-suppressing effects dates back to 2000 BC. The components of Curcuma Longa are curcumin, demethoxycurcumin and bisdemethoxycurcumini known as curcuminoids. Although it changes according to its type and the region in which it is raised, its original color is deep orange-yellow [7]. As shown by recent academic studies, curcumin has anti-inflammatory, anti-mutagenic and anti-carcinogenic effects. It has a potential area of use as a cancer molecule. Besides, it also comes to the forefront with its antioxidant effect and cell death (apoptosis) regulating effect.