Synergistic effects of S-alkenylmercaptocysteine (CySSR) species derived from Allium tissue and selenium on inducing apoptosis in ER− breast cancer cells. (February 2020)

• Record Type: Journal Article
• Authors: Zhang, Wei; Tocmo, Restituto; Parkin, Kirk L.
• Is Part Of: Journal of functional foods. Volume 65(2020)
• Publication Date: 2020-02
• Subjects: Apoptosis -- Synergism -- S-alkenylmercaptocysteine -- Sodium selenite -- Allium; CySSR cysteine-mixed disulfide conjugate -- CySSA S-allylmercaptocysteine -- CySSPe S-1-propenylmercaptocysteine -- CySH cysteine -- CySSCy cystine -- GSH glutathione (reduced) -- Se sodium selenite -- GSK glycogen synthase kinase -- JNK c-Jun NH2-terminal kinase -- MTT 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide -- DTNB 5, 5′-dithiobis(2-nitrobenzoate) -- ROS reactive oxygen species -- SSZ sulfasalazine -- xC- cystine/glutamate antiporter -- ER estrogen receptor -- OSC organosulfur compounds -- ACSO S-alk(en)yl-l-cysteine sulfoxides -- IC50 the half maximal inhibitory concentration -- Akt protein kinase B -- FITC fluorescein isothiocyanate -- PI propidium iodide -- Bax Bcl-2-associated X protein -- Bak Bcl-2 homologous antagonist killer -- H2Se hydrogen selenide -- RSH conjugate thiols; Functional foods -- Analysis -- Periodicals; Food -- Biotechnology -- Periodicals; Nutrition -- Periodicals; 613.2
• DOI: 10.1016/j.jff.2020.103786
• Languages: English
• ISSNs: 1756-4646

Abstract

Graphical abstract: Highlights: CySSR + Se show synergistic anticancer effects. CySSR + Se upregulated GSK3 and activated JNK pathway to induce apoptosis. CySSR reductive metabolites activated Se as H2 Se to contribute on apoptosis induction. CySSPe is similarly potent as the well-studied CySSA in signaling apoptosis. Abstract: 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 Na2 SeO3 (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.