A Bioactively Modified Fatty Acid Improves Survival and Impairs Metastasis in Preclinical Models of Acute Leukemia

• Published in: Clinical cancer research 2006-06, Vol.12 (11), p.3525-3531
• Main Authors: IVERSEN, Per O, SØRENSEN, Dag R, TRONSTAD, Karl J, GUDBRANDSEN, Oddrun A, RUSTAN, Arild C, BERGE, Rolf K, DREVON, Christian A
• Format: Article
• Language: English
• Subjects: Acute leukemia; Animals; Antineoplastic agents; apoptosis; Apoptosis - drug effects; Biological and medical sciences; Diet; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Enzyme Activation - drug effects; Fatty Acids, Unsaturated - administration & dosage; Humans; Leukemia, Promyelocytic, Acute - drug therapy; Leukemia-Lymphoma, Adult T-Cell - drug therapy; Leukemic Infiltration - diagnosis; matrix metalloproteinase; Matrix Metalloproteinases - drug effects; Medical sciences; Neoplasm Metastasis; Pharmacology. Drug treatments; polyunsaturated fatty acid; rat; Rats; Structure-Activity Relationship; Sulfides - administration & dosage; Survival Rate; Transplantation, Heterologous; Xenograft Model Antitumor Assays
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-05-2802

Purpose: Polyunsaturated fatty acids (PUFA) and the sulfur-substituted fatty acid tetradecylthioacetic acid (TTA) inhibit proliferation and induce apoptosis in lymphoma and leukemic cell lines, but it is unknown if they can modify leukemogenesis in the intact organism. Experimental Design: We now examined the effects of PUFA and TTA in rats transplanted with either acute promyelocytic leukemia or acute T-cell leukemia. The rats were randomized to isoenergetic diets containing either lard (control), ω3 (n-3) PUFA, or TTA. Results: Whereas TTA prolonged survival ( P < 0.05) in both types of rat leukemia, n-3 PUFA had no significant effect compared with controls. Only TTA inhibited ( P < 0.05) leukemic infiltration in the bone marrow and spleen, probably due to apoptosis of the leukemic cells. Plasma metalloproteinase activity, a marker of metastatic activity, was significantly reduced in TTA-fed rats only. Conclusions: Dietary intake of TTA, but not of n-3 PUFA, in rats with acute leukemia, prolonged their survival. TTA intake was also associated with reduced leukemic cell burden as well as diminished extramedullar dissemination. TTA represents a modified fatty acid that exerts unique effects on malignant hematopoietic cells, and the present study indicates that TTA may have a therapeutic potential in patients with acute leukemias.