Ramesh G, Das U N
Division of Internal Medicine, Clinical Immunology and Biochemistry, L.V. Prasad Eye Institute, Hyderabad, India.
Cancer Lett. 1998 Jan 30;123(2):207-14. doi: 10.1016/s0304-3835(97)00426-6.
Earlier studies performed both by us and by others have demonstrated that some n-3 and n-6 fatty acids can inhibit the growth of tumour cells in vitro. Though studies done with various types of oils rich in n-3 and n-6 fatty acids did show that the tumour incidence and growth can be modified, there were relatively few studies wherein the anti-tumour effects of individual free fatty acids were studied. Here we present results which suggest that free fatty acids (oleic acid (OA), linoleic acid (LA), alpha-linolenic acid (ALA), gamma-linolenic acid (GLA), arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) can inhibit the growth of methylcholanthrene-induced sarcoma cells (Meth-A cells) in vitro. The order of potency of various fatty acids on the growth of Meth-A cells was DHA > ALA > EPA > AA > GLA > LA > OA and their ID50 values were 10, 20, 35, 45, 68, 73 and 110 microg/ml/1 x 10(4) cells, respectively. These results indicate that the inhibitory action of different types of n-3, n-6 and n-9 fatty acids on Meth-A cells does not depend on their unsaturation. Vitamin E could partially block the cytotoxicity of these fatty acids indicating a possible role for free radicals. GLA, AA and EPA augmented the generation of superoxide anion and lipid peroxidation in Meth-A cells indicating a possible correlation between the ability of fatty acids to augment free radicals and their tumoricidal action. In an in vivo study, it was observed that OA, LA, ALA, GLA and EPA can prolong the survival of Meth-A-bearing mice when given intraperitoneally. Of all the fatty acids tested, surprisingly, LA was found to be the most potent in enhancing the survival of the tumour-bearing animals at all the concentrations tested. Thus, these studies suggest that free fatty acids can inhibit Meth-A tumour cell proliferation both in vitro and in vivo.
我们和其他人早期进行的研究均已证明，一些n-3和n-6脂肪酸在体外可抑制肿瘤细胞的生长。尽管对富含n-3和n-6脂肪酸的各类油脂进行的研究确实表明肿瘤发生率和生长情况可被改变，但其中研究单个游离脂肪酸抗肿瘤作用的研究相对较少。在此我们呈现的结果表明，游离脂肪酸（油酸（OA）、亚油酸（LA）、α-亚麻酸（ALA）、γ-亚麻酸（GLA）、花生四烯酸（AA）、二十碳五烯酸（EPA）和二十二碳六烯酸（DHA））在体外可抑制甲基胆蒽诱导的肉瘤细胞（Meth-A细胞）的生长。不同脂肪酸对Meth-A细胞生长的效力顺序为DHA > ALA > EPA > AA > GLA > LA > OA，其半数抑制浓度（ID50）值分别为10、20、35、45、68、73和110微克/毫升/1×10⁴个细胞。这些结果表明，不同类型的n-3、n-6和n-9脂肪酸对Meth-A细胞的抑制作用并不取决于其不饱和程度。维生素E可部分阻断这些脂肪酸的细胞毒性，表明自由基可能发挥作用。GLA、AA和EPA可增强Meth-A细胞中超氧阴离子的生成和脂质过氧化，表明脂肪酸增强自由基的能力与其杀肿瘤作用之间可能存在关联。在一项体内研究中，观察到当腹腔注射时，OA、LA、ALA、GLA和EPA可延长荷Meth-A小鼠的生存期。在所有测试的脂肪酸中，令人惊讶的是，在所有测试浓度下，LA在提高荷瘤动物生存期方面最为有效。因此，这些研究表明游离脂肪酸在体外和体内均可抑制Meth-A肿瘤细胞增殖。
