Abstract

Plenty of evidence supports the health effects exerted by dietary supplements containing phytochemicals, but the actual efficacy and safety of their combinations have been seldom experimentally evaluated. On this basis, we investigated in vitro the antioxidant/antineoplastic efficacy and anti-aging activity of a dietary supplement containing sulforaphane (SFN), a sulfur-isothiocyanate present in broccoli, combined with the patented extract Fernblock® XP (FB), obtained from the tropical fern Polypodium leucotomos. We evaluated the effect of SFN and FB, alone or in combination, on migration ability, matrix metalloproteinases (MMP) production, neoangiogenic potential and inflammasome activation in human WM115 and WM266-4 melanoma cells. Moreover, the effects on MMPs and reactive oxygen species production, and IL-1β secretion were studied in human normal keratinocytes. The SFN/FB combination inhibited melanoma cell migration in vitro, MMP-1, -2, -3, and -9 production, inflammasome activation and IL-1β secretion more efficiently than each individual compound did. In normal keratinocytes, SFN/FB was more efficient than SFN or FB alone in inhibiting MMP-1 and -3 production and IL-1β secretion in the presence of a pro-inflammatory stimulus such as TNF-α. The potential use of SFN/FB based supplements for the prevention of skin aging and as adjuvants in the treatment of advanced melanoma is suggested.

Highlights

  • Complex extracts or single compounds derived from plants have attracted considerable attention as potential preventive or therapeutic agents in chronic diseases pathogenically related to oxidative stress and/or inflammation

  • We investigated whether the effects exerted by individual administrations of SFN or Fernblock® XP (FB) to melanoma cells and normal keratinocytes in vitro could be enhanced if the cells were simultaneously exposed to both the compounds

  • We observed that the WM266-4 metastatic cells grew faster than the counterpart (WM115 cells) originated by the primary tumor, and that the separate addition of either SFN or FB reduced to a similar extent the growth of both the melanoma cell lines, independently from the degree of malignity

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Summary

Introduction

Complex extracts or single compounds derived from plants have attracted considerable attention as potential preventive or therapeutic agents in chronic diseases pathogenically related to oxidative stress and/or inflammation. It should be underlined that the compounds showing antioxidant properties (either endogenous or diet-derived) once inside the cells do not work independently, but as components of a complex organization, where each compound plays a specific role, and no one can perform the function of the entire team For this reason, supplementing a single antioxidant may alter the natural balance of antioxidants in tissues, and even produce paradoxical pro-oxidant effects [6]. The aim is to obtain multifunctional supplements able to integrate diets that, especially in some physiological (pregnancy, growth, exercise, aging) or pathological conditions (chronic inflammations, cancer, neurodegenerative disorders, etc.), do not satisfy the increased/changed body requirements Several of these combined supplements have been already put on the market, with the assumption that, since each individual component is known to induce some beneficial effects, the efficacy of their combination cannot be other than increased. Such studies on combined supplements could be essential to verify if the same effects usually obtained with high doses of one component could be obtained by combining lower doses of it with other components at relatively low doses, avoiding the potential cytotoxicity that can be associated to high doses

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