Iversen Per O, Sørensen Dag R, Tronstad Karl J, Gudbrandsen Oddrun A, Rustan Arild C, Berge Rolf K, Drevon Christian A
Department of Nutrition, University of Oslo, Norway.
Clin Cancer Res. 2006 Jun 1;12(11 Pt 1):3525-31. doi: 10.1158/1078-0432.CCR-05-2802.
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.
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), omega3 (n-3) PUFA, or TTA.
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.
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.
多不饱和脂肪酸（PUFA）和硫代取代脂肪酸十四烷基硫代乙酸（TTA）可抑制淋巴瘤和白血病细胞系的增殖并诱导其凋亡，但它们是否能在完整机体中改变白血病发生尚不清楚。
我们现在研究了PUFA和TTA对移植了急性早幼粒细胞白血病或急性T细胞白血病的大鼠的影响。将大鼠随机分为等能量饮食组，分别给予猪油（对照组）、ω-3（n-3）PUFA或TTA。
在两种类型的大鼠白血病中，TTA均延长了生存期（P < 0.05），而n-3 PUFA与对照组相比无显著影响。只有TTA抑制了（P < 0.05）骨髓和脾脏中的白血病浸润，这可能是由于白血病细胞的凋亡。血浆金属蛋白酶活性是转移活性的标志物，仅在喂食TTA的大鼠中显著降低。
急性白血病大鼠通过饮食摄入TTA而非n-3 PUFA可延长其生存期。摄入TTA还与白血病细胞负荷降低以及髓外播散减少有关。TTA是一种修饰脂肪酸，对恶性造血细胞具有独特作用，本研究表明TTA可能对急性白血病患者具有治疗潜力。
