Amino Acids

, Volume 41, Issue 1, pp 103–112

Allyl sulfur compounds and cellular detoxification system: effects and perspectives in cancer therapy

Review Article

DOI: 10.1007/s00726-010-0522-6

Cite this article as:
Melino, S., Sabelli, R. & Paci, M. Amino Acids (2011) 41: 103. doi:10.1007/s00726-010-0522-6

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.

Keywords

Organosulfur compoundsAlk(en)yl thiosulfateGarlicGlutathioneS-transferaseDetoxificationTumor

Abbreviations

2-PTS

Sodium-2-propenyl-thiosulfate

AMS

Allyl methyl sulfide

BBM

Brush-border membranes

CAR

Constitutive androstane receptor

GS-DNB

Glutathione-2,4-dinitrobenzene conjugate

DAS

Diallyl sulfide

DADS

Diallyl disulfide

DASO

Diallyl sulfoxide

DASO2

Diallyl sulfone

DATS

Diallyl trisulfide

DCF-DA

2′,7′-Dichlorodihydrofluorescein diacetate

DMDS

Dimethyl disulfide

DMH

Dimethyl-hydrazine

DTT

Dithiothreitol

GSH

Glutathione

GST

Glutathione S-transferase

HO 1

Heme oxygenase 1

MDR

Multidrug resistance

MRP

Multidrug resistance protein

MST

3-Mercaptopyruvate sulfurtransferase

NQO1

NAD(P)H: quinone oxidoreductase 1

Nrf2

NF-E2-related factor-2

Oatp4

Organic anion transporting polypeptide 4

OSCs

Organosulfur compounds

P450 s

Cytochrome P450 enzymes

P-gp

P-glycoprotein

ROS

Reactive oxygen species

SAC

S-allylcysteine

SAMC

S-allylmercaptocysteine

Trd

Thioredoxin reductase

Trx

Thioredoxin

TST

Thiosulfate sulfurtransferase

UGT

UDP-glucuronosyl transferase

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  1. 1.Department of Sciences and Chemical TechnologiesUniversity of Rome “Tor Vergata”RomeItaly