Combination of Juglone Along with Indomethacin Inhibits Proliferation and Alters Biochemical Parameters Against AOM/DSS Induced Colon Carcinogenesis Without Gastric Ulceration In Balb/C Mice.

Alagesan Seetha, Halagowder Devaraj ,Ganapasam Sudhandiran

Alagesan Seetha, Halagowder Devaraj ,Ganapasam Sudhandiran

Abstract

Colon cancer is the third most frequently diagnosed cancer worldwide. Indomethacin is one among the non-steroidal anti-inflammatory drugs (NSAIDs), and it has been reported to treat colon cancer. Still, exposure of indomethacin for long period causes gastric ulceration in humans. Hence, the present study is aimed to analyze the therapeutic effect of indomethacin and juglone against colon cancer without causing gastric ulceration, in Azoxymethane [AOM]/ Dextran sodium sulfate [DSS] induced adult male Balb/C mice. Colon cancer was induced by single intraperitoneal injection of AOM (10 mg/kg b.w) with 2% DSS in drinking water for a week and treated with indomethacin (2 mg/kg b.w) and juglone (0.5 mg/kg b.w) orally for three weeks, as alone and in combination (Indo + JUG). As a result, macroscopic examination on colonic tissue showed multiple nodules in AOM/DSS induced group and in gastric tissue, ulceration was observed in indomethacin treated group, these abnormalities were absent in indomethacin + juglone treated groups, which was confirmed by enzymatic, non-enzymatic biochemical parameters; the levels of Superoxide Dismutase [SOD], Catalase [CAT], Glutathione Peroxidase [GPx] and Vitamin-C&E was decreased upon induction and increased on treatment with indomethacin and juglone, the level of LPO in induced mice was increased and decreased upon treatment. Up regulated immune histopathological expression of proliferative marker PCNA (proliferating cell nuclear antigen) was observed in AOM/DSS induced group whereas the combination of both indomethacin + juglone showed decreased expression of PCNA. Thus, the drugs indomethacin and juglone, individually and together reduce the abnormal cell proliferation, while juglone effectively prevents indomethacin induced gastric ulceration, which act as a potential treatment for colon cancer.