2-2--azino-di-(3-ethylbenzothiazoline)-6-sulfonic-acid and Aberrant-Crypt-Foci

To explore fresh strategies in colorectal cancer (CRC) chemotherapy, we evaluated the capability of the ruthenium-phloretin complex in exterminating colon cancer by effectively addressing multiple apoptotic mechanisms on HT-29 cancer cells together with an animal model of colorectal cancer activated by 1,2-dimethylhydrazine and dextran sulfate sodium. Our current approach offers tangible evidence of the application of the ruthenium-phloretin complex in future chemotherapy. The complex triggers intrinsic apoptosis triggered by p53 and modulates the Akt/mTOR pathway along with other inflammatory biomarkers. The ruthenium-phloretin complex has been synthesized and successfully characterized by numerous spectroscopic methodologies accompanied by DPPH, FRAP, and ABTS assays assessing its antioxidant potential. Studies conducted in human cell lines revealed that the complex improved levels of p53 and caspase-3 while diminishing the activities of VEGF and mTOR, triggers apoptosis, and induces fragmentation of DNA in the HT-29 cells. Toxicity studies were conducted to identify the therapeutic doses of the novel complex in animal models. The outcomes of the in vivo report suggest that the complex was beneficial in repressing multiplicity of aberrant crypt foci as well as hyperplastic lesions and also promoted increased levels of CAT, SOD, and glutathione. In addition, the ruthenium-phloretin complex was able to control cell proliferation and boosted apoptotic outbursts in cancer cells associated with the increase in cellular response towards Bax while diminishing responses towards Bcl-2, NF-

Topics: Aberrant Crypt Foci; Animals; Antioxidants; Apoptosis; bcl-2-Associated X Protein; Benzothiazoles; Biphenyl Compounds; Cell Proliferation; Cell Survival; Colon; Colonic Neoplasms; DNA; Female; Free Radical Scavengers; HT29 Cells; Humans; Kidney; Male; Matrix Metalloproteinase 9; Mice, Inbred BALB C; NF-kappa B; Oxidation-Reduction; Phloretin; Picrates; Ruthenium; Spectroscopy, Fourier Transform Infrared; Sulfonic Acids; Toxicity Tests

Oxidative stress has been proposed to be involved in colorectal cancer development. Many dark pigments of plants have potent oxidative stress preventive properties. In this study, unpolished Thai rice was assessed for antioxidant activity using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) methods. Red strain unpolished Thai rice was also administered to rats exposed to azoxymethane (AOM) for induction of aberrant crypt foci (ACF). Serum malondialdehyde (MDA) and ferric reducing antioxidant power (FRAP) were investigated for cellular oxidative stress and serum antioxidants, respectively. Red pigment unpolished Thai rice demonstrated high antioxidant activity and was found to significantly and dose dependently decrease the total density and crypt multiplicity of ACF. Consumption of Thai rice further resulted in high serum antioxidant activity and low MDA cellular oxidative stress. Interestingly, the density of ACF was strongly related to MDA at r=0.964, while it was inversely related with FRAP antioxidants (r=-0.915, p<0.001). The results of this study suggest that the consumption of red strain of unpolished Thai rice may exert potentially beneficial effects on colorectal cancer through decrease in the level of oxidative stress.

Topics: Aberrant Crypt Foci; Animals; Antioxidants; Azoxymethane; Benzothiazoles; Biphenyl Compounds; Colorectal Neoplasms; Male; Malondialdehyde; Oryza; Oxidative Stress; Phytotherapy; Picrates; Plant Extracts; Rats; Rats, Sprague-Dawley; Sulfonic Acids; Thiazoles