The targeting mechanism of DHA ligand and its conjugate with Gemcitabine for the enhanced tumor therapy.

Abstract

Docosahexaenoic acid (DHA), an omega-3 C22 natural fatty acid serving as a precursor for metabolic and biochemical pathways, was reported as a targeting ligand of anticancer drugs. However, its tumor targeting ability and mechanism has not been claimed. Here we hypothesized that the uptake of DHA by tumor cells is related to the phosphatidylethanolamine (PE) contents in cell membranes. Thus, in this manuscript, the tumor-targeting ability of DHA was initially demonstrated in vitro and in vivo on different tumor cell lines by labeling DHA with fluorescence dyes. Subsequently, the tumor targeting ability was then correlated with the contents of PE in cell membranes to study the uptake mechanism. Further, DHA was conjugated with anticancer drug gemcitabine (DHA-GEM) for targeted tumor therapy. Our results demonstrated that DHA exhibited high tumor targeting ability and PE is the main mediator, which confirmed our hypothesis. The DHA-GEM displayed enhanced therapeutic efficacy than that of GEM itself, indicating that DHA is a promising ligand for tumor targeted therapy.

• Authors: Siwen Li, Jingyi Qin, Caiping Tian, Jie Cao, Guissi Fida, Zhaohui Wang, Haiyan Chen, Zhiyu Qian, Wei R Chen, Yueqing Gu
• Journal: Oncotarget (Oncotarget) Vol. 5 Issue 11 Pg. 3622-35 (Jun 15 2014) ISSN: 1949-2553 [Electronic] United States
• PMID: 25004114 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Antimetabolites, Antineoplastic
• Ligands
• Phosphatidylethanolamines
• Deoxycytidine
• Docosahexaenoic Acids
• phosphatidylethanolamine
• Gemcitabine

Topics

• Animals
• Antimetabolites, Antineoplastic (administration & dosage, chemistry, pharmacokinetics)
• Breast Neoplasms (drug therapy, metabolism)
• Cell Line, Tumor
• Deoxycytidine (administration & dosage, analogs & derivatives, chemistry, pharmacokinetics)
• Docosahexaenoic Acids (administration & dosage, chemistry, pharmacokinetics)
• Female
• Hep G2 Cells
• Humans
• Ligands
• Liver Neoplasms (drug therapy, metabolism)
• MCF-7 Cells
• Mice
• Mice, Nude
• Molecular Targeted Therapy
• Phosphatidylethanolamines (metabolism)
• Random Allocation
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays
• Gemcitabine