Antiproliferative and apoptotic-inducing potential of ellagic acid against 1,2-dimethyl hydrazine-induced colon tumorigenesis in Wistar rats

• Published in: Molecular and cellular biochemistry Vol. 388; no. 1-2; pp. 157 - 172
• Main Authors: Umesalma, Syed, Nagendraprabhu, Ponnuraj, Sudhandiran, Ganapasam
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.03.2014; Springer; Springer Nature B.V
• Subjects: 1,2-Dimethylhydrazine; Acids; Animals; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Biochemistry; Biomedical and Life Sciences; Biotransformation; Cardiology; Cell Proliferation - drug effects; Cell Transformation, Neoplastic - drug effects; Colon; Colon - pathology; Colon cancer; Colonic Neoplasms - chemically induced; Colonic Neoplasms - drug therapy; Cyclin D1 - biosynthesis; Detoxification; Ellagic acid; Ellagic Acid - pharmacology; Enzymes; Health aspects; Life Sciences; Male; Mast Cells - pathology; Matrix Metalloproteinase 2 - biosynthesis; Matrix Metalloproteinase 9 - biosynthesis; Medical Biochemistry; Oncology; Proliferating Cell Nuclear Antigen - biosynthesis; Rats; Rats, Wistar; Rodents; Tumor proteins; Tumor Suppressor Protein p53 - biosynthesis; Tumors; Colon cancer; Proliferation; Dimethylhydrazine; Ellagic acid; Apoptosis
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-013-1907-0

Colon cancer remains one of the major worldwide causes of cancer-related morbidity and mortality in Western countries and is increasingly common in Asia. Ellagic acid (EA), a major component of polyphenol possesses attractive remedial features. The aim of this study is to divulge the potential effect of EA during 1,2-dimethyl hydrazine (DMH)-induced colon cancer in male Wistar albino rats. The rats were segregated into four groups: group I, control rats; group II, rats received EA (60 mg/kg b.wt./day, orally); rats in group III, induced with DMH (20 mg/kg b.wt.) subcutaneously for 15 weeks; DMH-induced group IV rats were initiated with EA treatment. Colon of the rats treated with DMH exhibited higher glycoconjugates and proliferation index such as elevated expressions of argyrophilic nucleolar organizing regions (AgNORs), proliferating cell nuclear antigen (PCNA), cyclin D1, matrix metalloproteins (MMP-2 and -9), and mast cells. DMH induction also increased phase I-metabolizing enzymes with simultaneous decrease in the phase II detoxifying enzymes. In contrast, dietary administration of EA significantly ( p  < 0.05) down regulated the proliferation index and restored back the levels of biotransformation enzymes. The carcinogenic insult also altered the expression of pro-apoptotic protein p53, whereas dietary EA administration significantly ( p  < 0.01) up regulates p53 expression to further induce apoptotic pathway. Ultrastructural changes in colon were also in accord with the above aberrations. Overall findings suggested that the suppression of colon cancer by EA in vivo involves inhibition of cell proliferation, activation of apoptosis, and efficient detoxification.