Chueh Pin-Ju, Wu Lian-Ying, Morré Dorothy M, Morré D James
Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USA.
Biofactors. 2004;20(4):235-49.
Capsaicin and the principal green tea catechin, (-)-epigallocatechin-3-gallate (EGCg), target tNOX, a tumor (cancer)-specific surface hydroquinone (NADH) oxidase with protein disulfide-thiol interchange activity (ECTO-NOX protein). Accordingly vector-forced over expression of tNOX in MCF-10A mammary epithelia or COS cells that lack tNOX or in COS cells that underexpress tNOX enhanced the susceptibility of growth and apoptosis to both EGCg and capsaicin. Additionally, the tNOX-transfected MCF-10A cells proliferated in Matrigel, a measure of invasiveness. In contrast, oligomeric antisense tNOX DNA abrogated growth inhibition by EGCg and capsaicin and reduced anchorage-dependent growth of HeLa (human cervical carcinoma) cells that naturally overexpress tNOX. The findings show cell surface expression of tNOX as both necessary and sufficient for the cellular anticancer activities attributed to both EGCg and capsaicin.
辣椒素和主要的绿茶儿茶素,(-)-表没食子儿茶素-3-没食子酸酯(EGCg),作用于tNOX,一种具有蛋白质二硫键-硫醇交换活性的肿瘤(癌症)特异性表面对苯二酚(NADH)氧化酶(ECTO-NOX蛋白)。因此,在缺乏tNOX的MCF-10A乳腺上皮细胞或COS细胞中,或在tNOX表达不足的COS细胞中,通过载体强制过表达tNOX,增强了细胞对EGCg和辣椒素生长及凋亡的敏感性。此外,转染tNOX的MCF-10A细胞在基质胶中增殖,这是侵袭性的一种衡量指标。相反,寡聚反义tNOX DNA消除了EGCg和辣椒素对生长的抑制作用,并降低了天然过表达tNOX的HeLa(人宫颈癌)细胞的贴壁依赖性生长。这些发现表明,tNOX的细胞表面表达对于EGCg和辣椒素的细胞抗癌活性而言既是必要的也是充分的。