Concomitant supplementation of lycopene and eicosapentaenoic acid inhibits the proliferation of human colon cancer cells

J Nutr Biochem. 2009 Jun;20(6):426-34. doi: 10.1016/j.jnutbio.2008.05.001. Epub 2008 Aug 15.

Abstract

Several studies indicated that people who live in the Mediterranean region have very low rates of chronic diseases such as cardiovascular disease and cancer. It is well known that Mediterranean-style diet is rich in vegetables, tomato, fruit, fish and olive oil. These important dietary components may contribute to lower risk of cancer. Lycopene, a major component in tomato, exhibited potential anticarcinogenic activity. Previous studies showed that consumption of fish containing eicosapentaenoic acid (EPA) correlated with reduced risk of cancer. However, the combined effects of lycopene and EPA on the proliferation of human colon cancer have not been studied well yet. Thus, we investigated the anticancer properties and therapeutic potential of lycopene and EPA in human colon cancer HT-29 cells. In this study, we determined the combined effects of lycopene and EPA on the proliferation of human colon cancer HT-29 cells. We demonstrated that low concentration of lycopene and EPA could synergistically inhibit the proliferation of colon cancer cells. The inhibitory mechanism was associated with suppression of phosphatidylinositol 3-kinase/Akt signaling pathway. Furthermore, treatment of lycopene and EPA also synergistically blocked the activation of downstream mTOR molecule. Immunocytochemical staining results revealed that lycopene and EPA could also up-regulate the expression of apoptotic proteins such as Bax and Fas ligand to suppress cell survival. In conclusion, our novel findings suggest that lycopene and EPA synergistically inhibited the growth of human colon cancer HT-29 cells even at low concentration. The inhibitory effects of lycopene and EPA on cell proliferation of human colon cancer HT-29 cells were, in part, associated with the down-regulation of the PI-3K/Akt/mTOR signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticarcinogenic Agents / administration & dosage*
  • Anticarcinogenic Agents / pharmacology
  • Apoptosis
  • Carotenoids / administration & dosage*
  • Carotenoids / pharmacology
  • Cell Proliferation*
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology*
  • Down-Regulation
  • Eicosapentaenoic Acid / administration & dosage*
  • Eicosapentaenoic Acid / pharmacology
  • Fas Ligand Protein / metabolism
  • HT29 Cells
  • Humans
  • Lycopene
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protein Kinases / metabolism
  • TOR Serine-Threonine Kinases
  • bcl-2-Associated X Protein / metabolism

Substances

  • Anticarcinogenic Agents
  • BAX protein, human
  • Fas Ligand Protein
  • bcl-2-Associated X Protein
  • Carotenoids
  • Eicosapentaenoic Acid
  • Protein Kinases
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Lycopene