Abstract

6-(methylsulfinyl) hexyl isothiocyanate (6-MITC), is the main bioactive compound present in Wasabia japonica rhizome. Several scientific studies have shown that 6-MITC possesses interesting antimicrobial, anti-inflammatory, antiplatelet and antioxidant properties which therefore suggested us it could have an interesting chemopreventive potential. In a recent publication, we demonstrated, in two different leukemia cell lines, its ability to modulate several mechanisms supporting its antitumor activity. For this reason, we thought useful to continue the research, by investigating the potential antimutagenic activity of 6-MITC and thus better define its profile as a possible chemopreventive agent. 6-MITC antimutagenic effect against two known mutagenic agents: the clastogen Mitomycin C (MMC) and the aneuplodogen Vinblastine (VINB), was analyzed, in terms of micronuclei frequency decrease, after short- and long- time treatment on TK6 human cells, using a new automated protocol of the “In Vitro Mammalian Cell Micronucleous Test” by flow cytometry. The results showed a different behavior of the isothiocyante. In particular, 6-MITC was unable to counteract the MMC genotoxicity, but when it was associated with VINB a statistically significant decrease in the micronuclei frequency was registered. Overall, the results obtained suggest a potential antimutagenic activity of 6-MITC, in particular against the aneuploidogen agents. This ability, to inhibit or counteract the mutations at the cellular level has a great therapeutic value and it represents a mechanism through a chemopreventive agent can express its activity.

Highlights

  • 6-(Methylsulfinyl) hexil isothiocyanate (6-MITC) is the main bioactive compound present in Wasabia japonica, a plant belonging to the Brassicaceae family, called “Japanese radish”

  • Dimethyl sulfoxide (DMSO), Ethanol, Ethylenediaminetetraacetic acid (EDTA), Fetal Bovine Serum (FBS), L-Glutamine (L-GLU), Mitomycin C (MMC), Nonidet, Penicillin-Streptomycin solution (PS), Potassium Chloride, Potassium Dihydrogen Phosphate, Roswell Park Memorial Institute (RPMI) 1640 medium, Vinblastine (VINB),Water bpc grade, Sodium Chloride, Sodium Hydrogen Phosphate, Guava Nexin Reagent, Guava ViaCount Reagent, RNase A, SYTOX Green, 7-aminoactinomycinD (7-AAD)

  • Short-Term Treatment (3h+23h) In order to select the concentrations to be used in the following experiments, we, first, evaluated the cytotoxic and cytostatic potential of 6-MITC after 3h treatment followed by 23h of recovery in complete medium at different concentrations (0, 2, 4, 8, 16, 32, and 64μM)

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Summary

Introduction

6-(Methylsulfinyl) hexil isothiocyanate (6-MITC) is the main bioactive compound present in Wasabia japonica, a plant belonging to the Brassicaceae family, called “Japanese radish”. 6-MITC Antimutagenic and Chemopreventive Properties studies have shown that 6-MITC in particular, possesses interesting antimicrobial (Hirokuni et al, 1998; Ko et al, 2016), anti-inflammatory (Uto et al, 2005; Uto et al, 2007; Uto et al, 2012), antiplatelet (Morimitsu et al, 2000) and antioxidant (Mizuno et al, 2011) properties. These results suggested us a potential interest 6-MITC as a chemopreventive agent. If the mutation occurs in a somatic cell it could lead to premature aging, damage to the immune system and promote the development of chronic degenerative diseases, such as cancer (Basu, 2018)

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