Abstract
Isothiocyanates (ITCs) show strong activity against numerous human tumors. Five structurally diverse ITCs were tested in vivo using the zebrafish embryos 6 and 48 h post-fertilization (hpf). The survival rate, hatching time, and gross morphological changes were assessed 24, 48, and 72 h after treatment with all compounds in various doses (1–10 µM). As a result, we selected a phosphonate analog of sulforaphane (P-ITC; 1–3 µM) as a non-toxic treatment for zebrafish embryos, both 6 and 48 hpf. Furthermore, the in vivo anti-cancerogenic studies with selected 3 µM P-ITC were performed using a set of cell lines derived from the brain (U87), cervical (HeLa), and breast (MDA-MB-231) tumors. For the experiment, cells were labeled using red fluorescence dye Dil (1,1′-Dioctadecyl-3,3,3′,3′-Tetramethylindocarbocyanine, 10 μg/mL) and injected into the hindbrain ventricle, yolk sac region and Cuvier duct of zebrafish embryos. The tumor size measurement after 48 h of treatment demonstrated the significant inhibition of cancer cell growth in all tested cases by P-ITC compared to the non-treated controls. Our studies provided evidence for P-ITC anti-cancerogenic properties with versatile activity against different cancer types. Additionally, P-ITC demonstrated the safety of use in the living organism at various stages of embryogenesis.
Highlights
Isothiocyanates (ITCs; sulfur-containing substances) are naturally occurring small molecules formed from glucosinolate precursors in cruciferous vegetables, including cabbage, kale, broccoli, cauliflower, Brussels sprouts and kohlrabi [1]
Regulation of apoptosis by ITC is accomplished through the mitochondrial release of cytochrome c, Bcl-2 family regulation, MAPK signaling and subsequent activation of caspase −3 and −9 [38,39]
The data confirmed the anti-tumor effect of P-ITC, which was previously studied in the murine breast cancer model and the results suggested that P-ITC has broader activity in the cancer tissue context and can actively inhibit various tumors growth
Summary
Isothiocyanates (ITCs; sulfur-containing substances) are naturally occurring small molecules formed from glucosinolate precursors in cruciferous vegetables, including cabbage, kale, broccoli, cauliflower, Brussels sprouts and kohlrabi [1]. It was already shown that both natural and synthetic ITCs display anti-carcinogenic activity by affecting multiple mechanisms, including apoptosis, metastasis, vascularization, cell cycle, oxidative stress and epigenetic mechanisms [2,3] (Figure 1). Cells 2021, 10, x FOR PEER REVIEW Figure 1.
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