2-2--azino-di-(3-ethylbenzothiazoline)-6-sulfonic-acid and Colonic-Neoplasms

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

In the human diet, the consumption of fresh fruits and vegetables is important in maintaining good health and in preventing chronic diseases. It is known that plant-derived food is a powerful source of chemopreventive molecules, i.e. antioxidants, and spinach (Spinacia oleracea L., Chenopodiaceae) possesses a wide range of metabolites with such biological activity. Plant stress response could lead to the production of metabolites with high value for human health and this could be a tool to enhance the production of molecules with antioxidant activity in plants.. Data reported in this paper confirm the antioxidant properties of spinach plants, and show a strong antiproliferative activity of leaf extract on HT-29 human cell line. Besides, the hypoxic stress seems to affect the pool of antioxidant molecules present in spinach leaves, as verified by means of HPLC-MS/MS analysis and the aluminium chloride and ABTS assays.. Our findings represent a basis for improving the biological and pharmacological properties of spinach plants, including the use of different growth conditions to modulate the phytocomplex profile of spinach.

Topics: Adaptation, Physiological; Adenocarcinoma; Agriculture; Antineoplastic Agents, Phytogenic; Antioxidants; Benzothiazoles; Colonic Neoplasms; HT29 Cells; Humans; Neoplasms; Oxygen; Phytotherapy; Plant Extracts; Plant Leaves; Spinacia oleracea; Stress, Physiological; Sulfonic Acids; Vegetables