Supplementation of fish oil augments efficacy and attenuates toxicity of 5-fluorouracil in 1,2-dimethylhydrazine dihydrochloride/dextran sulfate sodium-induced colon carcinogenesis
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5-Fluorouracil (5-FU) is used for the treatment of colorectal cancer, but has low therapeutic response rate and severe side effects. Recently, fish oil (FO) rich in n-3 polyunsaturated fatty acids has been preferred to chemosensitize tumor cells to anticancer drugs. Therefore, the current study is designed to evaluate chemotherapeutic efficacy and toxicity profile of 5-FU in combination with FO in 1,2-dimethylhydrazine dihydrochloride/dextran sulfate sodium (DMH/DSS)-induced colon cancer model.
The therapeutic efficacy of 5-FU along with FO was analyzed through assessment of survival rate, tumor burden, volume, serum sialic acid levels, cytokeratin 19 (CK19) expression and index of cell proliferation such as cell cycle progression. Toxicological aspects were evaluated by standard functional and structural parameters related to spleen, gastrointestinal, liver and kidney.
In the present study, 5-FU in combination with FO increased the survival rate in carcinogen-treated animals. Synergism of 5-FU and FO was also reflected in significant inhibition in tumor growth and serum sialic acid levels in DMH/DSS model. Moreover, the combination dosage significantly augmented the inhibition of cell cycle progression, as shown by CK19 expression. Additionally, FO ameliorated hematologic depression, gastrointestinal, hepatic and renal toxicity caused by 5-FU as substantiated by a marked improvement in structural and functional alterations of these organs.
The supplementation of FO is potentially a promising option for increasing the therapeutic potential and mitigating the side effects of 5-FU.
Keywords5-Fluorouracil (5-FU) Fish oil (FO) n-3 Polyunsaturated fatty acids (PUFAs) Colorectal cancer (CRC) Biomarkers of carcinogenesis Chemotherapeutic toxicity
1,2-Dimethylhydrazine dihydrochloride/dextran sulfate sodium
n-3 Polyunsaturated fatty acids
Total sialic acid
Lipid-associated sialic acid
Hank’s balanced salt solution
Statistical package for social sciences
This work was supported by a grant from Department of Science and Technology (DST), Government of India (Ref. No. SR/SO/BB-0138/2012), India. The authors would like to acknowledge DST-Innovation in Science Pursuit for Inspired Research as Ms. Isha Rani is SRF-DST INSPIRE (IF10173). The authors also acknowledge the assistance from University Grants Commission as the department is supported under UGC SAP programme. The authors would also like to acknowledge Mrs. Sandhya, Senior Technician, CSIC Department, Postgraduate Institute of Medical Education and Research, Chandigarh, for her assistance in flow cytometric estimations.
Conflict of interest
The authors declare that there is no conflict of interest.
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