Investigation of the effects of palladium complex on 1,2-dimethylhydrazine-induced on colon cancer in mice

Colon cancer is the third most common cancer in the world and the second most common cancer in terms of mortality. This situation necessitates the development of new therapeutic approaches for the prevention and treatment of the disease. Although the in vitro anticancer effects of palladium (Pd) complexes are known, they have not been sufficiently investigated in vivo, especially at the level of molecular mechanisms. In this doctoral thesis study, the effects of a newly synthesised Pd complex in 1,2-dimethylhydrazine (DMH)-induced colon cancer model were investigated at molecular, biochemical, histopathological and haematological levels. In the study, 90 male Balb/C mice were divided into 6 groups (Control, Pd-I, Pd-II, DMH, DMH+Pd-I and DMH+Pd-II) and the experiment was carried out for 150 days. In the experimental study, colon cancer model was induced by administering DMH (once a week for a total of 8 doses, subcutaneously) at a dose of 20 mg/kg to mice. In the treatment groups, Pd complex was administered orally every other day at doses of 1 mg/kg (Pd-I) and 2 mg/kg (Pd-II). Macroscopic and histopathological examinations revealed that a large number of polyps and tumours developed in DMH-treated mice, whereas the number of these formations decreased when administered together with Pd complexes. Western blot analyses showed an increase in Bcl-2, PI3K/AKT/mTOR protein levels and a decrease in Caspase-3 levels in DMH group. On the other hand, a significant decrease in Bcl-2, PI3K/AKT/mTOR protein levels and an increase in Caspase-3 were observed in the groups treated with Pd complexes, especially in the Pd-II group (p<0.05). In biochemical analyses, DMH administration caused a significant increase in serum ALT, AST, BUN and creatinine levels, while these parameters approached control levels in Pd-I and Pd-II groups (p<0.05). In haematological analyses, while DMH administration caused deterioration in RBC, WBC and PLT values, Pd complex administration had a corrective effect on these parameters (p<0.05). In conclusion, Pd complex suppressed DMH-induced colorectal carcinogenesis process, activated apoptotic mechanisms by inhibiting PI3K/Akt/mTOR signalling pathway and prevented biochemical/hematological deterioration. These findings suggest that Pd complex may be a promising agent in the treatment of colon cancer.