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01-01-2005 | Original Article

Docosahexaenoic acid enhances the susceptibility of human colorectal cancer cells to 5-fluorouracil

Authors: Gabriella Calviello, Fiorella Di Nicuolo, Simona Serini, Elisabetta Piccioni, Alma Boninsegna, Nicola Maggiano, Franco O. Ranelletti, Paola Palozza

Published in: Cancer Chemotherapy and Pharmacology | Issue 1/2005

Abstract

Purpose

Powerful growth-inhibitory action has been shown for n-3 polyunsaturated fatty acids against colon cancer cells. We have previously described their ability to inhibit proliferation of colon epithelial cells in patients at high risk of colon cancer. In the work reported here we investigated the ability of docosahexaenoic acid (DHA) to potentiate the antineoplastic activity of 5-fluorouracil (5-FU) in p53-wildtype (LS-174 and Colo 320) and p53-mutant (HT-29 and Colo 205) human colon cancer cells.

Methods

When in combination with DHA, 5-FU was used at concentrations ranging from 0.1 to 1.0 μM, much lower than those currently found in plasma patients after infusion of this drug. Similarly, the DHA concentrations (≤10 μM) used in combination with 5-FU were lower than those widely used in vitro and known to cause peroxidative effects in vivo.

Results

Whereas the cells showed different sensitivity to the growth-inhibitory action of 5-FU, DHA reduced cell growth independently of p53 cellular status. DHA synergized with 5-FU in reducing colon cancer cell growth. The potentiating effect of DHA was attributable to the enhancement of the proapoptotic effect of 5-FU. DHA markedly increased the inhibitory effect of 5-FU on the expression of the antiapoptotic proteins BCL-2 and BCL-X_L, and induced overexpression of c-MYC which has recently been shown to drive apoptosis and, when overexpressed, to sensitize cancer cells to the action of proapoptotic agents, including 5-FU.

Conclusion

Our results indicate that DHA strongly increases the antineoplastic effects of low concentrations of 5-FU. Overall, the results suggest that combinations of low doses of the two compounds could represent a chemotherapeutic approach with low toxicity.

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Title: Docosahexaenoic acid enhances the susceptibility of human colorectal cancer cells to 5-fluorouracil
Authors: Gabriella Calviello
Fiorella Di Nicuolo
Simona Serini
Elisabetta Piccioni
Alma Boninsegna
Nicola Maggiano
Franco O. Ranelletti
Paola Palozza
Publication date: 01-01-2005
Publisher: Springer-Verlag
Published in: Cancer Chemotherapy and Pharmacology / Issue 1/2005
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-004-0846-6

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Abstract

Purpose

Methods

Results

Conclusion

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