EVALUATION OF THE EFFICACY OF FUCOIDAN NANOPARTICLES IN EXPERIMENTAL COLON CARCINOGENESIS USING IN VITRO AND IN VIVO STUDIES

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2022
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The study was taken up to explore the antitumour potentials of fucoidan and FNPs in dimethyl hydrazine dihydrochloride (DMH) induced colon carcinogenesis in rat model. Cancer incidence is on the rise, necessitating the use of immediate, effective medications to combat the disease. Natural products have recently attracted a lot of attention for cancer chemotherapy because of their low toxicity and side effects. In the present study, ionic gelation method was used to synthesize the FNPs. The synthesized FNPs were characterized for their size, shape and morphology by various techniques including particle size analyzer (DLS), Zeta potential (ELS), FTIR, TEM, SEM and XRD. The entrapment efficiency of NPs was performed to observe their stability and sustained release. Human colon cancer cell line HT-29 was used to assess the anticancer potentials of the NPs. The effect of FNPs was compared with the standard drug 5- Fluorouracil (5-FU) to observe their cytotoxic potency. In vivo studies were conducted in wistar rats using DMH@ 40 mg / kg b. wt. by i.p. route to induce colon carcinogenesis. Confirmation of tumour induction was performed by using ACF development as biomarker. The rats were then treated with fucoidan and fucoidan NPs at 10 and 5 mg/kg b.wt. i.p. respectively on every two days. At the end of the experimental period, blood and serum samples were collected for haematology and serum biochemistry. Liver and colon tissues were collected for analysing redox status. Immunohistochemical studies were performed for specific markers of colon epithelium PCNA (proliferation marker), Bcl-2, Bax, VEGF, Carcino-embryonic antigen (CEA), Cytokeratin 20 (CK20) and Vimentin. Real time quantification was carried out to measure the expression levels of genes Bax, Bcl-2, AKT, PI3K, PTEN and mTOR with β-actin as endogenous control. Histopathological changes in the colon, kidney and liver were analysed.
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