The Anti-Tumoral Potential of Phosphonate Analog of Sulforaphane in Zebrafish Xenograft Model.
Magdalena Rudzinska-RadeckaLukasz JanczewskiAnna GajdaCharlotte GimpelMalgorzata Chmielewska-KrzesinskaKrzysztof WasowiczPiotr PodlaszPublished in: Cells (2021)
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.
Keyphrases
- papillary thyroid
- cell cycle arrest
- endothelial cells
- squamous cell
- induced apoptosis
- squamous cell carcinoma
- mitral valve
- combination therapy
- pulmonary artery
- pulmonary hypertension
- white matter
- young adults
- risk assessment
- transcription factor
- single molecule
- quantum dots
- childhood cancer
- computed tomography
- signaling pathway
- subarachnoid hemorrhage
- resting state
- pi k akt
- genome wide identification