Novel Broccoli Sulforaphane-Based Analogues Inhibit the Progression of Pancreatic Cancer without Side Effects

• Main Authors: Christina Georgikou, Laura Buglioni, Maximilian Bremerich, Nico Roubicek, Libo Yin, Wolfgang Gross, Carsten Sticht, Carsten Bolm, Ingrid Herr
• Format: Article
• Language: English
• Published: MDPI AG 2020-05-01
• Series: Biomolecules
• Subjects: bioactive agents; drug development; microRNA signaling; pancreatic cancer; NCI-60; sulforaphane
• Online Access: https://www.mdpi.com/2218-273X/10/5/769

The naturally occurring isothiocyanate sulforaphane, found in <i>Brassicaceae</i> vegetables, is promising in cancer treatment, e.g., by the normalization of enhanced levels of NF-κB-signaling in tumor stem cells. We chemically synthesized seven sulforaphane analogues by substitution of the sulfinyl group (S(O)) to either sulfimidoyl (S(NR)) or sulfonimidoyl (S (O) (NR)) groups, and characterized them in the cell lines of pancreatic cancer and several other tumor entities, including the NCI-60 cell panel. MTT and colony forming assays, flow cytometry, immunohistochemistry, microRNA arrays, bioinformatics, tumor xenotransplantation, and Kaplan Meier survival curves were performed. Compared to sulforaphane, the analogue <b>SF102</b> was most efficient in inhibition of viability, colony formation, tumor growth, and the induction of apoptosis, followed by <b>SF134.</b> Side effects were not observed, as concluded from the body weight and liver histology of chick embryos and survival of <i>C. elegans</i> nematodes. Among 6659 differentially regulated microRNAs, miR29b-1-5p, and miR-27b-5p were downregulated by sulforaphane compared to controls, but upregulated by <b>SF102</b> and <b>SF134</b> compared to sulforaphane, suggesting differential signaling. Each substance was involved in the regulation of several NF-κB-related target genes. In conclusion, sulforaphane analogues are promising for the development of highly active new drugs in cancer treatment.