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Potential role of organic sulfur compounds from Allium species in cancer prevention and therapy

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Abstract

Phytochemical research has revealed that organic sulfur-containing compounds (OSCs) from Allium species exert biological effects, that might be beneficial in the treatment or prevention of a range of diseases, such as infections, cardiovascular and metabolic affections, cancers and related indispositions. Focusing physiological activities of these compounds in the context of cancer, it became clear from both epidemiological studies in men and experimental studies in diverse models, that the OSCs have a strong potential to prevent or to treat cancers even with selectivity against non-neoplastic cells. Though underlying mechanisms are not yet fully understood, several parts of their modes and mechanisms of action were elucidated: Pivotal molecular targets of as well chemoprevention as chemotherapy are metabolic, transporter or repair enzymes strongly affecting cell death, proliferation and formation of metastases. Accordingly effects are not restricted to the run of cell death programs, but they moreover comprise the strongly interdepending immune and inflammatory systems. Respectively, several hypotheses exist which are based on chemical properties of sulfur as the “pharmacophor” of the compounds appearing in up to ten different oxidation states (−2 to +6). Hence compounds can undergo redox-reactions and electrostatic interactions, making reactive oxygen species (ROS) a key feature of their mechanisms of action.

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Abbreviations

(A)GE:

(Aged) garlic extract

AHQR:

Agency for Healthcare Research and Quality

Akt:

Member of the protein kinase B-family

AML:

Acute myeloid leukemia

AMS:

Allyl methyl sulfide

AMTS:

MATS allyl methyl trisulfide

ARE:

Anti-oxidant response element

ATR:

Ataxia-telangiectasia mutated and Rad3 related

Bcl-2:

B-cell lymphoma 2

BPH:

Benign prostatic hyperplasia

Cdk1:

Cyclin dependent kinase1

Chk1:

Checkpoint kinase1

COX:

Cyclooxygenase

CYP450:

Cytochrome P450

DADS:

Diallyl disulfide

DAS:

Diallyl sulfide

DATS:

Diallyl trisulfide

DATTS:

Diallyl tetrasulfide

DMTS:

Dimethyl trisulfide

DPDS:

Dipropyl disulfide

DPS:

Dipropyl sulfide

DPTS:

Dipropyl trisulfide

DPTTS:

Dipropyl tetrasulfide

DU145:

Human prostate cancer cells

ERK:

Extracellular signal-regulated kinases

Ets-1:

Erythroblastosis virus E26 oncogene homolog 1

γ-GCS:

γ-Glutamylcysteine synthetase

G(P)E:

Garlic (powder) extract

GO:

Garlic oil

GP:

Garlic powder

GST:

Glutathione-S-transferase

HDAC:

Histone deacetylase

HEK:

Human embryonic kidney cells

HIF:

Hypoxia-inducible factors

HL60:

Human leukemia cells

HO1:

Heme oxygenase 1

HUVEC:

Human umbilical vein endothelial cells

IAP:

Inhibitor of apoptosis protein family

ICAM:

Intercellular adhesion molecule

IL:

Interleukin

iNOS:

Inducible nitric oxide synthase

JNK:

c-Jun-terminal kinases

LDL:

Low density proteins

LPS:

lipopolysaccharide

MAPK:

Mitogen-activated protein kinases

MDR:

Multidrug resistance

NCI:

National Cancer Institute

NFκB:

Nuclear factor kappa B

NK:

Natural killer cells

Nox:

NADPH-oxidases

NQO1:

NAD(P)H:quinone oxidoreductase 1

Nrf2:

Nuclear factor E2-related factor 2

OO:

Onion oil

OSC(s):

Organic sulfur compound(s)

p53:

Tumor suppressor protein (mass 53 kDa)

PBMCs:

Peripheral blood mononuclear cells

PC-3:

Human prostate cancer cells

P-gp:

Glycoprotein P

PI3:

Phosphatidylinositol

PMS:

Propyl methyl sulfide

QR:

Quinone reductase

Ref:

Redox-factors

RNS:

Reactive nitrogen species

ROS:

Reactive oxygen species

SAC:

S-Allyl cysteine

SAMC:

S-Allyl mercaptocysteine

SH-SY5Y:

Human neuroblastoma cells

SOD:

Superoxide dismutase

SW480:

Human colon adenocarcinoma cells

TNF:

Tumor necrosis factor

UK:

United Kingdom

VEGF:

Vascular endothelial growth factor

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Acknowledgement

CS thanks the “Ministère de la Culture, de l’Enseignement supérieur et de la Recherche of Luxembourg” for financial support by providing a “Bourse de formation-recherche”. Moreover researchers are indebted to “Télévie”, the “Fondation de Recherche Cancer et Sang” and “Recherches Scientifiques” Luxembourg association. Likewise the authors thank “Een Häerz fir Kriibskrank Kanner” association, the Action Lions “Vaincre le Cancer”, the Foundation for Scientific Cooperation between Germany and Luxemburg, and the Saarland University for additional support.

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  1. Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Hôpital Kirchberg, 9, Rue Edward Steichen, Luxembourg, Luxemburg

    C. Scherer, M. Dicato & M. Diederich

  2. Bioorganic Chemistry, Saarland University, Saarbrücken, Germany

    C. Scherer & C. Jacob

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  1. C. Scherer
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  2. C. Jacob
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Scherer, C., Jacob, C., Dicato, M. et al. Potential role of organic sulfur compounds from Allium species in cancer prevention and therapy. Phytochem Rev 8, 349–368 (2009). https://doi.org/10.1007/s11101-009-9122-z

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