1. Asiatic acid abridges pre-neoplastic lesions, inflammation, cell proliferation and induces apoptosis in a rat model of colon carcinogenesis.
- Author
-
Siddique AI, Mani V, Renganathan S, Ayyanar R, Nagappan A, and Namasivayam N
- Subjects
- 1,2-Dimethylhydrazine toxicity, Aberrant Crypt Foci pathology, Animals, Apoptosis drug effects, Caspase 3 metabolism, Cell Proliferation drug effects, Colonic Neoplasms chemically induced, Colonic Neoplasms pathology, Cyclin D1 metabolism, Cytochrome P-450 Enzyme System metabolism, Disease Models, Animal, Down-Regulation drug effects, Liver drug effects, Liver enzymology, Male, Pentacyclic Triterpenes toxicity, Proliferating Cell Nuclear Antigen metabolism, Proto-Oncogene Proteins c-bcl-2 metabolism, Rats, Rats, Wistar, Up-Regulation drug effects, bcl-2-Associated X Protein metabolism, Colonic Neoplasms drug therapy, Pentacyclic Triterpenes therapeutic use
- Abstract
The utmost aim of this present study was to investigate the anti-inflammatory, antiproliferative and proapoptotic potential of Asiatic acid (AA) on 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis in experimental rats. Rats were divided into six groups and received modified pellet diet for 32 weeks. Group 1 served as control rats. Group 2 received AA (4 mg/kg b.w. p.o.). Group 3-6 rats received 15 DMH (20 mg/kg b.w., s.c.) injections once a week starting from the 4th week. Besides DMH, rats received AA (4 mg/kg b.w. p.o.) in group 4 starting 2 weeks before carcinogen treatment till the end of the last DMH; group 5 starting 2 days after last DMH till the end of the experiment; and group 6 throughout the experiment. Pre-neoplastic lesions, xenobiotic metabolizing enzymes, inflammation, cell proliferation and apoptotic markers were analysed in our study. Our results ascertained AA supplementation to DMH-exposed rats significantly decreased the incidence of aberrant crypt foci (ACF) and phase I xenobiotic enzymes; and increased the phase II xenobiotic enzymes and mucin content as compared to DMH-alone-exposed rats. Moreover the increased expressions of mast cells, argyrophilic nucleolar organizer regions (AgNORs), proliferating cell nuclear antigen (PCNA) and cyclin D1 observed in the DMH-alone-exposed rats were reverted and were comparable with those of the control rats, when treated with AA. Concordantly AA also induced apoptosis by downregulating the expression of Bcl-2 and upregulating Bax, cytochrome c, caspase-3 and -9 in the DMH-alone-exposed rats. Thus AA was able to inhibit DMH-induced colon carcinogenesis by detoxifying the carcinogen, decreasing the preneoplastic lesions by virtue of its anti-inflammatory, antiproliferative and proapoptotic effects. Therefore our findings suggest that AA could be used as an effective chemopreventive agent against DMH induced colon carcinogenesis., (Copyright © 2017 Elsevier B.V. All rights reserved.)
- Published
- 2017
- Full Text
- View/download PDF