Docosahexaenoic-Acid enhances the susceptibility of human colorectal cancer cells to 5-Fluorouracil.

Gabriella Calviello, Simona Serini, Fiorella Di Nicuolo, Elisabetta Piccioni, Alma Boninsegna Lucarelli, Nicola Giuseppe Maggiano, Franco Oreste Ranelletti, Paola Palozza

Research output: Contribution to journalArticlepeer-review

76 Citations (Scopus)

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 microM, much lower than those currently found in plasma patients after infusion of this drug. Similarly, the DHA concentrations (< or =10 microM) 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-XL, 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.
Original languageEnglish
Pages (from-to)12-20
Number of pages9
JournalCancer Chemotherapy and Pharmacology
Publication statusPublished - 2005

Keywords

  • 5-Fluorouracil
  • adjuvant therapy
  • colon cancer cells
  • n-3 PUFA

Fingerprint

Dive into the research topics of 'Docosahexaenoic-Acid enhances the susceptibility of human colorectal cancer cells to 5-Fluorouracil.'. Together they form a unique fingerprint.

Cite this