Deciphering the biochemical and molecular mechanism underlying the in vitro and in vivo chemotherapeutic efficacy of ruthenium quercetin complex in colon cancer. Issue 6 (5th March 2018)

• Record Type: Journal Article
• Authors: Roy, Souvik; Das, Rituparna; Ghosh, Balaram; Chakraborty, Tania
• Is Part Of: Molecular carcinogenesis. Volume 57:Issue 6(2018)
• Page Start: 700
• Page End: 721
• Publication Date: 2018-03-05
• Subjects: colon carcinogenesis -- in vitro study -- ruthenium quercetin complex -- structural characterization -- toxicity study; Carcinogenesis -- Molecular aspects -- Periodicals; 616.994071
• DOI: 10.1002/mc.22792
• Languages: English
• ISSNs: 0899-1987

Abstract

Abstract : Flavonoids are the most investigated phytochemicals due to their pharmacological and therapeutic activities. Their ability to chelate with metal ions has resulted in the emergence of a new category of molecules with a broader spectrum of pharmacological activities. In this study, the ruthenium quercetin complex has been synthesized and anticancer activity has been evaluated on a well‐defined model of DMH followed by DSS induced rat colon cancer and on human colon cancer cell line HT‐29. The characterizations accomplished through UV‐visible, NMR, IR, Mass spectra and XRD techniques, and antioxidant activity was assessed by DPPH, FRAP, and ABTS methods. In vitro study confirmed that the complex increased p53 expression, reduced VEGF and mTOR expression, apoptosis induction, and DNA fragmentation in the HT‐29 cells. Acute and subacute toxicity study was also assessed and results from in vivo study revealed that complex was efficient to suppress ACF multiplicity and hyperplastic lesions and elevated the CAT, SOD, and glutathione levels. Furthermore, the complex was found to decrease cell proliferation and increased apoptotic events in tumor cells correlates upregulation of p53 and Bax and downregulation of Bcl2 expression. Our findings from the in vitro and in vivo study support the continued investigation of ruthenium quercetin complex possesses a potential chemotherapeutic activity against colon cancer and was efficient in reducing ACF multiplicity, hyperplastic lesions in the colon tissues of rats by inducing apoptosis. Abstract : Synthesis, characterization of ruthenium quercetin complex by UV, IR, NMR, Mass, XRD, and SEM. Free radical scavenging activity of quercetin was found to increase after complexation and the complex was found to interact with (Calf Thymus) CT‐DNA. Ruthenium quercetin complex inhibits cell viability, arrests the cells at G0/G1 phase, upregulated p53 and downregulated VEGF, and mTOR expression in HT‐29 cells. The complex reduces the ACF multiplicity, elevated SOD, CAT, and glutathione levels, inhibits cell proliferation by increasing p53, Bax, and reducing Bcl2 expression.