Department of Food Science and Nutrition, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310029, P R China.
Lipids Health Dis. 2010 Sep 24;9:106. doi: 10.1186/1476-511X-9-106.
Some polyunsaturated fatty acids (PUFAs), if not all, have been shown to have tumoricidal action, but their exact mechanism(s) of action is not clear. In the present study, we observed that n-6 PUFA linoleic acid (LA) inhibited tumor cell growth at high concentrations (above 300 μM); while low concentrations (100-200 μM) promoted proliferation. Analysis of cell mitochondrial membrane potential, reactive oxygen species (ROS) formation, malondialdehyde (MDA) accumulation and superoxide dismutase (SOD) activity suggested that anti-cancer action of LA is due to enhanced ROS generation and decreased cell anti-oxidant capacity that resulted in mitochondrial damage. Of the three cell lines tested, semi-differentiated colorectal cancer cells RKO were most sensitive to the cytotoxic action of LA, followed by undifferentiated colorectal cancer cell line (LOVO) while the normal human umbilical vein endothelial cells (HUVEC) were the most resistant (the degree of sensitivity to LA is as follows: RKO > LOVO > HUVEC). LA induced cell death was primed by mitochondrial apoptotic pathway. Pre-incubation of cancer cells with 100 μM LA for 24 hr enhanced sensitivity of differentiated and semi-differentiated cells to the subsequent exposure to LA. The relative resistance of LOVO cells to the cytotoxic action of LA is due to a reduction in the activation of caspase-3. Thus, LA induced cancer cell apoptosis by enhancing cellular oxidant status and inducing mitochondrial dysfunction.
一些多不饱和脂肪酸（PUFAs），如果不是全部，已经被证明具有杀肿瘤作用，但它们的确切作用机制尚不清楚。在本研究中，我们观察到 n-6 多不饱和脂肪酸亚油酸（LA）在高浓度（高于 300 μM）时抑制肿瘤细胞生长；而低浓度（100-200 μM）则促进增殖。细胞线粒体膜电位、活性氧（ROS）形成、丙二醛（MDA）积累和超氧化物歧化酶（SOD）活性分析表明，LA 的抗癌作用是由于增强了 ROS 的产生和降低了细胞抗氧化能力，导致线粒体损伤。在所测试的三种细胞系中，半分化结直肠癌细胞 RKO 对 LA 的细胞毒性作用最敏感，未分化结直肠癌细胞系（LOVO）次之，而正常的人脐静脉内皮细胞（HUVEC）最耐受（对 LA 的敏感性程度如下：RKO>LOVO>HUVEC）。LA 诱导的细胞死亡是由线粒体凋亡途径引发的。将癌细胞用 100 μM LA 预孵育 24 小时可增强分化和半分化细胞对随后暴露于 LA 的敏感性。LOVO 细胞对 LA 细胞毒性作用的相对抗性是由于 caspase-3 的激活减少所致。因此，LA 通过增强细胞氧化状态和诱导线粒体功能障碍诱导癌细胞凋亡。
