Chemoprotective effect of theanine in 1,2-dimethylhydrazine-induced colorectal cancer in rats via suppression of inflammatory parameters

Abstract

Colorectal cancer is considered as a major cancer among all types of cancers, especially in developed countries. The colorectal cancer has few to no symptoms and mostly the tumor is often diagnosed in the later stage of cancer. Oxidative stress and inflammatory reaction play an important role in the expansion and the progression of colorectal cancer. Theanine exhibits antioxidant and anti-inflammatory potential against various diseases. As a result of its antioxidant and anti-inflammatory nature, in this study, we estimated the protective effect of theanine against 1,2-dimethylhydrazine (DMH)-induced colorectal cancer and explored the possible mechanism. Subcutaneous injection (35 mg/kg) of DMH was used to induce colorectal cancer in rats. Rats were divided into different groups and were orally administrated with theanine (5, 10, and 20 mg/kg) for 16 weeks. Body weight, tumor size, and average tumor weight were determined at the end of the experimental study. Biochemical tests, antioxidant properties, phase I and phase II enzymes, and inflammatory mediators were estimated. The mRNA expression of p38 mitogen-activated protein kinase (p38MAPK), p53, and apoptosis was also estimated at the end of the experimental study. Theanine significantly (p < .001) increases the body weight and suppressed the average tumor size in DMH-induced colorectal cancer. Similarly, it significantly (p < .001) reduces the level of prostaglandin (PGE₂ ), cyclooxygenase-2 (COX-2), and myeloperoxidase (MPO). It also decreases the oxidative stress by suppressing the level of malonaldehyde (MDA) and enhancing the level of SOD, GPx, CAT, and GR. Theanine considerably reduced tumor markers, such as lactate dehydrogenase (LDH) and carcinoembryonic antigen (CEA) and phase I and phase II enzymes in a dose-dependent manner. It also significantly (p < .001) suppressed the expression of p38-MAPK, p-53, caspase-3, caspase-8, and caspase-9 in a dose-dependent manner. Collectively, we can say that theanine exhibited the chemoprotective effect against the colorectal cancer by inhibiting the oxidative stress and inflammatory reaction. PRACTICAL APPLICATIONS: Theanine is the major amino acid phytoconstituent of green tea. It has a potent antioxidant activity and is also able to protect against various oxidative damage. In this experimental study, theanine exhibits a protective effect against colorectal cancer by suppressing the oxidative stress and inflammatory reaction. The results suggest that theanine may be used for colorectal cancer prevention and treatment.

Keywords: MAPK-myeloperoxidase; antioxidant; apoptosis; colorectal cancer; inflammation; theanine.