Miller Aine, Stanton Catherine, Devery Rosaleen
School of Biotechnology, Dublin City University, Dublin 9, Ireland.
Anticancer Res. 2002 Nov-Dec;22(6C):3879-87.
Dietary conjugated linoleic acid (CLA) has been shown to reduce colon tumor incidence in rodents by mechanisms probably involving apoptosis. The aim of this study was to evaluate the effects of three commercial CLA preparations (pure c9, t11-CLA, pure t10, c12-CLA and a CLA mixture, containing 29.5% c9, t11 and 29% t10, c12-CLA) on caspase-dependent apoptosis in colon SW480 tumor cells. After 4 days incubation, all CLA-treated cells displayed an increase in caspase 3 (27-34%) and caspase 9 activities (37-47%), cleavage of pro-caspase 3 (32 kDa) to 17 and 12 kDa subunits, increased membrane annexin V levels and reduced expression of bcl-2 compared with untreated controls. Cytosolic cytochrome c was increased (p < 0.05) by all CLA preparations, with the t10, c12-CLA isomer being the most potent. The data indicate that t10, c12-CLA may be the more biologically active isomer for inhibition of colon tumor cell proliferation in vitro.
膳食共轭亚油酸(CLA)已被证明可通过可能涉及细胞凋亡的机制降低啮齿动物的结肠肿瘤发生率。本研究的目的是评估三种市售CLA制剂(纯c9,t11-CLA、纯t10,c12-CLA以及一种CLA混合物,含有29.5%的c9,t11和29%的t10,c12-CLA)对结肠SW480肿瘤细胞中半胱天冬酶依赖性细胞凋亡的影响。孵育4天后,与未处理的对照相比,所有CLA处理的细胞中半胱天冬酶3(增加27-34%)和半胱天冬酶9活性(增加37-47%)升高,前半胱天冬酶3(32 kDa)裂解为17 kDa和12 kDa亚基,膜联蛋白V水平增加,bcl-2表达降低。所有CLA制剂均使细胞溶质细胞色素c增加(p<0.05),其中t10,c12-CLA异构体最为有效。数据表明,t10,c12-CLA可能是体外抑制结肠肿瘤细胞增殖的更具生物活性的异构体。