Allyl sulfur compounds and cellular detoxification system: effects and perspectives in cancer therapy |
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Authors: | S Melino R Sabelli M Paci |
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Institution: | (1) Department of Sciences and Chemical Technologies, University of Rome “Tor Vergata”, via della Ricerca Scientifica, Rome, 00133, Italy |
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Abstract: | Natural organosulfur compounds (OSCs) have been shown to have chemopreventive effects and to suppress the proliferation of
tumor cells in vitro through the induction of apoptosis. The biochemical mechanisms underlying the antitumorigenic and anti-proliferative
effects of garlic-derived OSCs are not fully understood. Several modes of action of these compounds have been proposed, and
it seems likely that the rate of clearance of allyl sulfur groups from cells is a determinant of the overall response. The
aim of this review is to focus attention on the effects of natural allyl sulfur compounds on the cell detoxification system
in normal and tumor cells. It has been already reported that several natural allyl sulfur compounds induce chemopreventive
effects by affecting xenobiotic metabolizing enzymes and inducing their down-activation. Moreover, different effects of water-
and oil-soluble allyl sulfur compounds on enzymes involved in the detoxification system of rat tissues have been observed.
A direct interaction of the garlic allyl sulfur compounds with proteins involved in the detoxification system was studied
in order to support the hypothesis that proteins possessing reactive thiol groups and that are involved in the detoxification
system and in the cellular redox homeostasis, are likely the preferential targets of these compounds. The biochemical transformation
of the OSCs in the cell and their adducts with thiol functional groups of these proteins, could be considered relevant events
to uncover the anticancer properties of the allyl sulfur compounds. Although additional studies, using proteomic approaches
and transgenic models, are needed to identify the molecular targets and modes of action of these natural compounds, the allyl
sulfur compounds can represent potential ideal agents in anticancer therapy, either alone or in association with other antitumor
drugs. |
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