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Synergistic effects of S-alkenylmercaptocysteine (CySSR) species derived from Allium tissue and selenium on inducing apoptosis in ER− breast cancer cells
Journal of Functional Foods ( IF 5.6 ) Pub Date : 2020-01-14 , DOI: 10.1016/j.jff.2020.103786
Wei Zhang , Restituto Tocmo , Kirk L. Parkin

S-Allylmercaptocysteine (CySSA) from garlic and its onion analog S-1-propenylmercaptocysteine (CySSPe) show potential anti-cancer abilities. In this study, apoptosis induction by these two S-alk(en)lymercaptocysteine (CySSR) analogs in combination with Na2SeO3 (Se) was investigated in MDA-MD-231 breast cancer cells. CySSA and CySSPe alone did not affect cell viability, whereas CySSPe + Se and CySSA + Se showed dose-dependent reduction in cell viability. Synergistic effect was confirmed by isobologram analysis. Annexin-V staining and flow cytometric analysis revealed induction of apoptosis. Mechanistically, CySSR + Se upregulated GSK-3α/β and activated p53 to trigger apoptosis. Both CySSR + Se activated JNK pathway at an early stage, but only CySSPe + Se exhibited sustained JNK activation. Inhibition of the cystine/glutamate (xC-) antiporter by sulfasalazine attenuated the antiproliferative effects of CySSR + Se suggesting the involvement of xC- in CySSR + Se induced apoptosis. This study indicates that the onion analogue CySSPe was similarly as effective as the major studied garlic analogue CySSA in apoptosis induction in ER breast cancer cells.



中文翻译:

的协同效应小号-alkenylmercaptocysteine(CySSR)物种衍生自组织和硒在ER诱导凋亡-乳腺癌细胞

大蒜中的S-烯丙基巯基半胱氨酸(CySSA)及其洋葱类似物S -1-丙烯基巯基半胱氨酸(CySSPe)具有潜在的抗癌能力。在这项研究中,这两个S- alk(en)巯基半胱氨酸(CySSR)类似物与Na 2 SeO 3组合诱导细胞凋亡(Se)在MDA-MD-231乳腺癌细胞中进行了研究。单独的CySSA和CySSPe不会影响细胞活力,而CySSPe + Se和CySSA + Se则显示出剂量依赖性的细胞活力降低。通过等效线图分析证实了协同作用。Annexin-V染色和流式细胞仪分析表明诱导凋亡。从机制上讲,CySSR + Se上调GSK-3α/β并激活p53触发凋亡。CySSR + Se都在早期激活了JNK通路,但只有CySSPe + Se表现出持续的JNK激活。胱氨酸/谷氨酸的抑制(X Ç - )通过逆向转运柳氮衰减CySSR +硒提示x的参与抗增殖作用Ç -在CySSR +硒-诱导凋亡。这项研究表明,洋葱模拟CySSPe也同样有效,因为在ER主要研究的大蒜模拟CySSA诱导细胞凋亡-乳腺癌细胞。

更新日期:2020-01-14
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