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Cancer Chemotherapy and Pharmacology

, Volume 74, Issue 2, pp 309–322 | Cite as

Supplementation of fish oil augments efficacy and attenuates toxicity of 5-fluorouracil in 1,2-dimethylhydrazine dihydrochloride/dextran sulfate sodium-induced colon carcinogenesis

  • Isha Rani
  • Kim Vaiphei
  • Navneet AgnihotriEmail author
Original Article

Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusion

The supplementation of FO is potentially a promising option for increasing the therapeutic potential and mitigating the side effects of 5-FU.

Keywords

5-Fluorouracil (5-FU) Fish oil (FO) n-3 Polyunsaturated fatty acids (PUFAs) Colorectal cancer (CRC) Biomarkers of carcinogenesis Chemotherapeutic toxicity 

Abbreviations

5-FU

5-Fluorouracil

FO

Fish oil

CRC

Colorectal cancer

DMH/DSS

1,2-Dimethylhydrazine dihydrochloride/dextran sulfate sodium

PUFAs

n-3 Polyunsaturated fatty acids

EPA

Eicosapentaenoic acid

DHA

Docosahexaenoic acid

TSA

Total sialic acid

LASA

Lipid-associated sialic acid

EDTA

Ethylenediaminetetraacetic acid

HBSS

Hank’s balanced salt solution

CK19

Cytokeratin 19

PE

Phycoerythrin

PI

Propidium iodide

b.w.

Body weight

GST

Glutathione-S-transferase

UGT

UDP-glucuronosyltransferase

SPSS

Statistical package for social sciences

Notes

Acknowledgments

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.

Supplementary material

280_2014_2497_MOESM1_ESM.docx (16.5 mb)
Supplementary material 1 (DOCX 537 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.Department of BiochemistryPanjab UniversityChandigarhIndia
  2. 2.Department of HistopathologyPost Graduate Institute of Medical Education and ResearchChandigarhIndia

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