title: Dose-dependent effects of R-sulforaphane isothiocyanate on the biology of human mesenchymal stem cells, at dietary amounts, it promotes cell proliferation and reduces senescence and apoptosis, while at anti-cancer drug doses, it has a cytotoxic effect.
abstract: Brassica vegetables are attracting a great deal of attention as healthy foods because of the fact that they contain substantial amounts of secondary metabolite glucosinolates that are converted into isothiocyanates, such as sulforaphane [(-)1-isothiocyanato-4R-(methylsulfinyl)-butane] (R-SFN), through the actions of chopping or chewing the vegetables. Several studies have analyzed the biological and molecular mechanisms of the anti-cancer activity of synthetic R,S-sulforaphane, which is thought to be a result of its antioxidant properties and its ability to inhibit histone deacetylase enzymes (HDAC). Few studies have addressed the possible antioxidant effects of R-SFN, which could protect cells from the free radical damage that strongly contribute to aging. Moreover, little is known about the effect of R-SFN on stem cells whose longevity is implicated in human aging. We evaluated the effects of R-SFN on the biology on human mesenchymal stem cells (MSCs), which, in addition to their ability to differentiate into mesenchymal tissues, support hematopoiesis, and contribute to the homeostatic maintenance of many organs and tissues. Our investigation found evidence that low doses of R-SFN promote MSCs proliferation and protect them from apoptosis and senescence, while higher doses have a cytotoxic effect, leading to the induction of cell cycle arrest, programmed cell death and senescence. The beneficial effects of R-SFN may be ascribed to its antioxidant properties, which were observed when MSC cultures were incubated with low doses of R-SFN. Its cytotoxic effects, which were observed after treating MSCs with high doses of R-SFN, could be attributed to its HDAC inhibitory activity. In summary, we found that R-SFN, like many other dietary supplements, exhibits a hormetic behavior; it is able to induce biologically opposite effects at different doses.
authors.affiliation: Department of Experimental Medicine, Biotechnology and Molecular Biology Section, Second University of Naples, Italy.
authors.forename: Fulvia
authors.initials: F
authors.lastname: Zanichelli
authors.forename: Stefania
authors.initials: S
authors.lastname: Capasso
authors.forename: Marilena
authors.initials: M
authors.lastname: Cipollaro
authors.forename: Eleonora
authors.initials: E
authors.lastname: Pagnotta
authors.forename: Maria
authors.initials: M
authors.lastname: Cartenì
authors.forename: Fiorina
authors.initials: F
authors.lastname: Casale
authors.forename: Renato
authors.initials: R
authors.lastname: Iori
authors.forename: Umberto
authors.initials: U
authors.lastname: Galderisi
mesh_terms: D000375:Aging / Q000187:drug effects*; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D059447:Cell Cycle Checkpoints; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002648:Child; D019587:Dietary Supplements; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013454:Sulfoxides; D013861:Thiocyanates / Q000494:pharmacology*
chemical_list: D016588:Anticarcinogenic Agents; D017879:Isothiocyanates; D013454:Sulfoxides; D013861:Thiocyanates; C037152:isothiocyanic acid; C016766:sulforaphane