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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

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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.

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Authors and Affiliations

  1. Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Temple University, Philadelphia, PA, USA

    Umberto Galderisi

  2. Department of Experimental Medicine, Biotechnology and Molecular Biology Section, Second University of Naples, Via Costantinopoli 16, 80138, Naples, Italy

    Fulvia Zanichelli, Stefania Capasso, Marilena Cipollaro, Maria Cartenì & Umberto Galderisi

  3. Human Health Foundation, Spoleto, Italy

    Umberto Galderisi

  4. Consiglio per la Ricerca e la Sperimentazione in Agricoltura (C.R.A.), Industrial Crop Research Centre, Bologna, Italy

    Eleonora Pagnotta & Renato Iori

  5. Department of Pediatrics “F. Fede”, Second University of Naples, Naples, Italy

    Fiorina Casale

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  1. Fulvia Zanichelli
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  2. Stefania Capasso
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  3. Marilena Cipollaro
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  4. Eleonora Pagnotta
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  5. Maria Cartenì
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  7. Renato Iori
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  8. Umberto Galderisi
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Correspondence to Umberto Galderisi.

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Zanichelli, F., Capasso, S., Cipollaro, M. et al. 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. AGE 34, 281–293 (2012). https://doi.org/10.1007/s11357-011-9231-7

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  • DOI: https://doi.org/10.1007/s11357-011-9231-7

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