Departments of Pharmacology, The Penn State Hershey Cancer Institute, The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033-0850, USA.
Nutr Cancer. 2013;65(6):891-9. doi: 10.1080/01635581.2013.802001.
In this study we demonstrated that Triticuside A, one of the flavonoid compounds isolated from wheat bran, induced apoptosis and inhibited proliferation of human breast cancer cells. Triticuside A inhibited the proliferation of human breast cancer cells (MCF-7 and MDA-MB-231) in a dose-dependent manner but barely showed cytotoxicity to the normal human fibroblasts. Triticuside A-induced apoptosis was accompanied by a significant decrease of Mcl-1 and Bcl-2 proteins and by an increase of cleavage of caspases-3, -7, -9, and PARP. Triticuside A also suppressed the level of phospho-Akt and its downstream targets, mTOR and P70 S6 kinase. LY294002, a specific inhibitor of PI3K, significantly enhanced the Triticuside A-induced apoptosis. Moreover LY294002 not only downregulated the level of phospho-Akt but also enhanced the inhibition of Mcl-1 expression when combined with Triticuside A. Our results demonstrate for the first time the specific apoptogenic activity of Triticuside A in tumor cells and involvement of the mitochondrial apoptosis pathway and Akt/mTOR signaling pathway. Thus, Triticuside A may be a potentially useful wheat bran component that can be used for prevention or treatment of breast cancer.
在这项研究中，我们证明了从麦麸中分离出来的黄酮类化合物之一 Triticuside A 能够诱导人乳腺癌细胞凋亡并抑制其增殖。Triticuside A 以剂量依赖的方式抑制人乳腺癌细胞（MCF-7 和 MDA-MB-231）的增殖，但对正常人类成纤维细胞几乎没有细胞毒性。Triticuside A 诱导的细胞凋亡伴随着 Mcl-1 和 Bcl-2 蛋白的显著减少，以及 caspase-3、-7、-9 和 PARP 的切割增加。Triticuside A 还抑制了磷酸化 Akt 及其下游靶标 mTOR 和 P70 S6 激酶的水平。PI3K 的特异性抑制剂 LY294002 显著增强了 Triticuside A 诱导的细胞凋亡。此外，当与 Triticuside A 联合使用时，LY294002 不仅下调了磷酸化 Akt 的水平，而且增强了对 Mcl-1 表达的抑制。我们的研究结果首次证明了 Triticuside A 在肿瘤细胞中具有特异性的促凋亡活性，并涉及线粒体凋亡途径和 Akt/mTOR 信号通路。因此，Triticuside A 可能是一种潜在有用的麦麸成分，可用于预防或治疗乳腺癌。
