Skip to main content

Advertisement

SpringerLink
Log in

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

  • Published:
Phytochemistry Reviews Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

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

References

  • Agarwal KC (1996) Therapeutic actions of garlic constituents. Med Res Rev 16:111–124. doi:10.1002/(SICI)1098-1128(199601)16:1<111::AID-MED4>3.0.CO;2-5

    PubMed  CAS  Google Scholar 

  • Agarwal MK, Iqbal M, Athar M (2007) Garlic oil ameliorates ferric nitrilotriacetate (Fe-NTA)-induced damage and tumor promotion: implications for cancer prevention. Food Chem Toxicol 45:1634–1640. doi:10.1016/j.fct.2007.02.029

    PubMed  CAS  Google Scholar 

  • Aggarwal BB, Shishodia S (2004) Suppression of the nuclear factor-kappa B activation pathway by spice-derived phytochemicals: reasoning for seasoning. Ann N Y Acad Sci 1030:434–441. doi:10.1196/annals.1329.054

    PubMed  CAS  Google Scholar 

  • Ambudkar SV, Dey S, Hrycyna CA, Ramachandra M, Pastan I, Gottesman MM (1999) Biochemical, cellular, and pharmacological aspects of the multidrug transporter. Annu Rev Pharmacol Toxicol 39:361–398. doi:10.1146/annurev.pharmtox.39.1.361

    PubMed  CAS  Google Scholar 

  • Antlsperger DS, Dirsch VM, Ferreira D, Su JL, Kuo ML, Vollmar AM (2003) Ajoene-induced cell death in human promyeloleukemic cells does not require JNK but is amplified by the inhibition of ERK. Oncogene 22:582–589. doi:10.1038/sj.onc.1206161

    PubMed  CAS  Google Scholar 

  • Antosiewicz J, Herman-Antosiewicz A, Marynowski SW, Singh SV (2006) c-Jun NH(2)-terminal kinase signaling axis regulates diallyl trisulfide-induced generation of reactive oxygen species and cell cycle arrest in human prostate cancer cells. Cancer Res 66:5379–5386. doi:10.1158/0008-5472.CAN-06-0356

    PubMed  CAS  Google Scholar 

  • Ariga T, Seki T (2006) Antithrombotic and anticancer effects of garlic-derived sulfur compounds: a review. Biofactors 26:93–103. doi:10.1002/biof.5520260201

    PubMed  CAS  Google Scholar 

  • Arora A, Seth K, Shukla Y (2004) Reversal of P-glycoprotein-mediated multidrug resistance by diallyl sulfide in K562 leukemic cells and in mouse liver. Carcinogenesis 25:941–949. doi:10.1093/carcin/bgh060

    PubMed  CAS  Google Scholar 

  • Arunkumar A, Vijayababu MR, Venkataraman P, Senthilkumar K, Arunakaran J (2006) Chemoprevention of rat prostate carcinogenesis by diallyl disulfide, an organosulfur compound of garlic. Biol Pharm Bull 29:375–379. doi:10.1248/bpb.29.375

    PubMed  CAS  Google Scholar 

  • Balasenthil S, Ramachandran CR, Nagini S (2001) S-allylcysteine, a garlic constituent, inhibits 7, 12-dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis. Nutr Cancer 40:165–172. doi:10.1207/S15327914NC402_13

    PubMed  CAS  Google Scholar 

  • Balasenthil S, Rao KS, Nagini S (2002) Apoptosis induction by S-allylcysteine, a garlic constituent, during 7, 12-dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis. Cell Biochem Funct 20:263–268. doi:10.1002/cbf.967

    PubMed  CAS  Google Scholar 

  • Barrett M (2004) The handbook of clinically tested remedies: botanical profiles—product and clinical trial information (Grape Seed—Valerian and Herbal Formulas). Haworth Press, Binghamton

  • Benkeblia N (2005) Free-radical scavenging capacity and antioxidant properties of some selected onions (Allium cepa L.) and garlic (Allium sativum L.) extracts. Braz Arch Biol Technol 48:753–759. doi:10.1590/S1516-89132005000600011

    CAS  Google Scholar 

  • Benkeblia N, Lanzotti V (2007) Allium thiosulfinates: chemistry, biological properties and their potential utilization in food preservation. Food 1:193–201

    Google Scholar 

  • Betteridge DJ (2000) What is oxidative stress? Metabolism 49:3–8. doi:10.1016/S0026-0495(00)80077-3

    PubMed  CAS  Google Scholar 

  • Block E (1992) The organosulfur chemistry of the genus Allium—implications for the organic chemistry of sulfur. Angew Chem Int Ed Engl 31:1135–1178. doi:10.1002/anie.199211351

    Google Scholar 

  • Blumberg J, Milbury P (2006) In: Bowman B, Russell R (eds) Present knowledge in nutrition. ILSI Press, Washington, DC, pp 361–370

  • Bottone FG Jr, Baek SJ, Nixon JB, Eling TE (2002) Diallyl disulfide (DADS) induces the antitumorigenic NSAID-activated gene (NAG-1) by a p53-dependent mechanism in human colorectal HCT 116 cells. J Nutr 132:773–778

    PubMed  CAS  Google Scholar 

  • Bush AI (2000) Metals and neuroscience. Curr Opin Chem Biol 4:184–191. doi:10.1016/S1367-5931(99)00073-3

    PubMed  CAS  Google Scholar 

  • Challier B, Perarnau JM, Viel JF (1998) Garlic, onion and cereal fibre as protective factors for breast cancer: a French case–control study. Eur J Epidemiol 14:737–747. doi:10.1023/A:1007512825851

    PubMed  CAS  Google Scholar 

  • Chan K, Kan YW (1999) Nrf2 is essential for protection against acute pulmonary injury in mice. Proc Natl Acad Sci USA 96:12731–12736. doi:10.1073/pnas.96.22.12731

    PubMed  CAS  Google Scholar 

  • Chan JM, Wang F, Holly EA (2005) Vegetable and fruit intake and pancreatic cancer in a population-based case–control study in the San Francisco bay area. Cancer Epidemiol Biomarkers Prev 14:2093–2097. doi:10.1158/1055-9965.EPI-05-0226

    PubMed  Google Scholar 

  • Chen C, Pung D, Leong V et al (2004) Induction of detoxifying enzymes by garlic organosulfur compounds through transcription factor Nrf2: effect of chemical structure and stress signals. Free Radic Biol Med 37:1578–1590. doi:10.1016/j.freeradbiomed.2004.07.021

    PubMed  CAS  Google Scholar 

  • Cheng G, Cao Z, Xu X, van Meir EG, Lambeth JD (2001) Homologs of gp91phox: cloning and tissue expression of Nox3, Nox4, and Nox5. Gene 269:131–140. doi:10.1016/S0378-1119(01)00449-8

    PubMed  CAS  Google Scholar 

  • Chu Q, Ling MT, Feng H et al (2006) A novel anticancer effect of garlic derivatives: inhibition of cancer cell invasion through restoration of E-cadherin expression. Carcinogenesis 27:2180–2189. doi:10.1093/carcin/bgl054

    PubMed  CAS  Google Scholar 

  • Clerkin JS, Naughton R, Quiney C, Cotter TG (2008) Mechanisms of ROS modulated cell survival during carcinogenesis. Cancer Lett 266:30–36. doi:10.1016/j.canlet.2008.02.029

    PubMed  CAS  Google Scholar 

  • Das A, Banik NL, Ray SK (2007) Garlic compounds generate reactive oxygen species leading to activation of stress kinases and cysteine proteases for apoptosis in human glioblastoma T98G and U87MG cells. Cancer 110:1083–1095. doi:10.1002/cncr.22888

    PubMed  CAS  Google Scholar 

  • Dashwood RH, Ho E (2007) Dietary histone deacetylase inhibitors: from cells to mice to man. Semin Cancer Biol 17:363–369. doi:10.1016/j.semcancer.2007.04.001

    PubMed  CAS  Google Scholar 

  • Davenport DM, Wargovich MJ (2005) Modulation of cytochrome P450 enzymes by organosulfur compounds from garlic. Food Chem Toxicol 43:1753–1762. doi:10.1016/j.fct.2005.05.018

    PubMed  CAS  Google Scholar 

  • Davis SR (2005) An overview of the antifungal properties of allicin and its breakdown products—the possibility of a safe and effective antifungal prophylactic. Mycoses 48:95–100. doi:10.1111/j.1439-0507.2004.01076.x

    PubMed  CAS  Google Scholar 

  • Delhalle S, Blasius R, Dicato M, Diederich M (2004) A beginner’s guide to NF-kappaB signaling pathways. Ann N Y Acad Sci 1030:1–13. doi:10.1196/annals.1329.002

    PubMed  CAS  Google Scholar 

  • Devrim E, Durak I (2007) Is garlic a promising food for benign prostatic hyperplasia and prostate cancer? Mol Nutr Food Res 51:1319–1323. doi:10.1002/mnfr.200600302

    PubMed  CAS  Google Scholar 

  • Dirsch VM, Gerbes AL, Vollmar AM (1998) Ajoene, a compound of garlic, induces apoptosis in human promyeloleukemic cells, accompanied by generation of reactive oxygen species and activation of nuclear factor kappa B. Mol Pharmacol 53:402–407

    PubMed  CAS  Google Scholar 

  • Dirsch VM, Antlsperger DS, Hentze H, Vollmar AM (2002) Ajoene, an experimental anti-leukemic drug: mechanism of cell death. Leukemia 16:74–83. doi:10.1038/sj.leu.2402337

    PubMed  CAS  Google Scholar 

  • Doulias PT, Barbouti A, Galaris D, Ischiropoulos H (2001) SIN-1-induced DNA damage in isolated human peripheral blood lymphocytes as assessed by single cell gel electrophoresis (comet assay). Free Radic Biol Med 30:679–685. doi:10.1016/S0891-5849(00)00511-6

    PubMed  CAS  Google Scholar 

  • Druesne N, Pagniez A, Mayeur C et al (2004) Diallyl disulfide (DADS) increases histone acetylation and p21(waf1/cip1) expression in human colon tumor cell lines. Carcinogenesis 25:1227–1236. doi:10.1093/carcin/bgh123

    PubMed  CAS  Google Scholar 

  • Elango EM, Asita H, Nidhi G, Seema P, Banerji A, Kuriakose MA (2004) Inhibition of cyclooxygenase-2 by diallyl sulfides (DAS) in HEK 293T cells. J Appl Genet 45:469–471

    PubMed  Google Scholar 

  • Feig DI, Reid TM, Loeb LA (1994) Reactive oxygen species in tumorigenesis. Cancer Res 54:1890s–1894s

    PubMed  CAS  Google Scholar 

  • Fidler IJ, Schroit AJ (1988) Recognition and destruction of neoplastic cells by activated macrophages: discrimination of altered self. Biochim Biophys Acta 948:151–173

    PubMed  CAS  Google Scholar 

  • Filomeni G, Aquilano K, Rotilio G, Ciriolo MR (2003) Reactive oxygen species-dependent c-Jun NH2-terminal kinase/c-Jun signaling cascade mediates neuroblastoma cell death induced by diallyl disulfide. Cancer Res 63:5940–5949

    PubMed  CAS  Google Scholar 

  • Finkel T, Holbrook NJ (2000) Oxidants, oxidative stress and the biology of ageing. Nature 408:239–247. doi:10.1038/35041687

    PubMed  CAS  Google Scholar 

  • Fisher CD, Augustine LM, Maher JM et al (2007) Induction of drug-metabolizing enzymes by garlic and allyl sulfide compounds via activation of constitutive androstane receptor and nuclear factor E2-related factor 2. Drug Metab Dispos 35:995–1000. doi:10.1124/dmd.106.014340

    PubMed  CAS  Google Scholar 

  • Fleischauer AT, Arab L (2001) Garlic and cancer: a critical review of the epidemiologic literature. J Nutr 131:1032S–1040S

    PubMed  CAS  Google Scholar 

  • Fukao T, Hosono T, Misawa S, Seki T, Ariga T (2004a) Chemoprotective effect of diallyl trisulfide from garlic against carbon tetrachloride-induced acute liver injury of rats. Biofactors 21:171–174. doi:10.1002/biof.552210135

    PubMed  CAS  Google Scholar 

  • Fukao T, Hosono T, Misawa S, Seki T, Ariga T (2004b) The effects of allyl sulfides on the induction of phase II detoxification enzymes and liver injury by carbon tetrachloride. Food Chem Toxicol 42:743–749. doi:10.1016/j.fct.2003.12.010

    PubMed  CAS  Google Scholar 

  • Galanis A, Pappa A, Giannakakis A, Lanitis E, Dangaj D, Sandaltzopoulos R (2008) Reactive oxygen species and HIF-1 signalling in cancer. Cancer Lett 266:12–20. doi:10.1016/j.canlet.2008.02.028

    PubMed  CAS  Google Scholar 

  • Galaris D, Skiada V, Barbouti A (2008) Redox signaling and cancer: the role of “labile” iron. Cancer Lett 266:21–29. doi:10.1016/j.canlet.2008.02.038

    PubMed  CAS  Google Scholar 

  • Gao CM, Takezaki T, Ding JH, Li MS, Tajima K (1999) Protective effect of allium vegetables against both esophageal and stomach cancer: a simultaneous case-referent study of a high-epidemic area in Jiangsu Province, China. Jpn J Cancer Res 90:614–621

    PubMed  CAS  Google Scholar 

  • Geng Z, Rong Y, Lau BH (1997) S-allyl cysteine inhibits activation of nuclear factor kappa B in human T cells. Free Radic Biol Med 23:345–350. doi:10.1016/S0891-5849(97)00006-3

    PubMed  CAS  Google Scholar 

  • Gonzalez CA, Pera G, Agudo A et al (2006) Fruit and vegetable intake and the risk of stomach and oesophagus adenocarcinoma in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST). Int J Cancer 118:2559–2566. doi:10.1002/ijc.21678

    PubMed  CAS  Google Scholar 

  • Guengerich FP (1988) Roles of cytochrome P-450 enzymes in chemical carcinogenesis and cancer chemotherapy. Cancer Res 48:2946–2954

    PubMed  CAS  Google Scholar 

  • Halliwell B, Gutteridge JM, Cross CE (1992) Free radicals, antioxidants, and human disease: where are we now? J Lab Clin Med 119:598–620

    PubMed  CAS  Google Scholar 

  • Hartwell LH, Weinert TA (1989) Checkpoints: controls that ensure the order of cell cycle events. Science 246:629–634. doi:10.1126/science.2683079

    PubMed  CAS  Google Scholar 

  • Hassan HT (2004) Ajoene (natural garlic compound): a new anti-leukaemia agent for AML therapy. Leuk Res 28:667–671. doi:10.1016/j.leukres.2003.10.008

    PubMed  CAS  Google Scholar 

  • Hassan ZM, Yaraee R, Zare N, Ghazanfari T, Sarraf Nejad AH, Nazori B (2003) Immunomodulatory affect of R10 fraction of garlic extract on natural killer activity. Int Immunopharmacol 3:1483–1489. doi:10.1016/S1567-5769(03)00161-9

    PubMed  CAS  Google Scholar 

  • Hawkins CL, Davies MJ (2002) Hypochlorite-induced damage to DNA, RNA, and polynucleotides: formation of chloramines and nitrogen-centered radicals. Chem Res Toxicol 15:83–92. doi:10.1021/tx015548d

    PubMed  CAS  Google Scholar 

  • Herman-Antosiewicz A, Singh SV (2004) Signal transduction pathways leading to cell cycle arrest and apoptosis induction in cancer cells by Allium vegetable-derived organosulfur compounds: a review. Mutat Res 555:121–131. doi:10.1016/j.mrfmmm.2004.04.016

    PubMed  CAS  Google Scholar 

  • Herman-Antosiewicz A, Powolny AA, Singh SV (2007a) Molecular targets of cancer chemoprevention by garlic-derived organosulfides. Acta Pharmacol Sin 28:1355–1364. doi:10.1111/j.1745-7254.2007.00682.x

    PubMed  CAS  Google Scholar 

  • Herman-Antosiewicz A, Stan SD, Hahm ER, Xiao D, Singh SV (2007b) Activation of a novel ataxia-telangiectasia mutated and Rad3 related/checkpoint kinase 1-dependent prometaphase checkpoint in cancer cells by diallyl trisulfide, a promising cancer chemopreventive constituent of processed garlic. Mol Cancer Ther 6:1249–1261. doi:10.1158/1535-7163.MCT-06-0477

    PubMed  CAS  Google Scholar 

  • Ho SE, Ide N, Lau BH (2001) S-allyl cysteine reduces oxidant load in cells involved in the atherogenic process. Phytomedicine 8:39–46. doi:10.1078/0944-7113-00005

    PubMed  CAS  Google Scholar 

  • Hong YS, Ham YA, Choi JH, Kim J (2000) Effects of allyl sulfur compounds and garlic extract on the expression of Bcl-2, Bax, and p53 in non small cell lung cancer cell lines. Exp Mol Med 32:127–134

    PubMed  CAS  Google Scholar 

  • Hosono T, Fukao T, Ogihara J et al (2005) Diallyl trisulfide suppresses the proliferation and induces apoptosis of human colon cancer cells through oxidative modification of beta-tubulin. J Biol Chem 280:41487–41493. doi:10.1074/jbc.M507127200

    PubMed  CAS  Google Scholar 

  • Howard EW, Ling MT, Chua CW, Cheung HW, Wang X, Wong YC (2007) Garlic-derived S-allylmercaptocysteine is a novel in vivo antimetastatic agent for androgen-independent prostate cancer. Clin Cancer Res 13:1847–1856. doi:10.1158/1078-0432.CCR-06-2074

    PubMed  CAS  Google Scholar 

  • Hsing AW, Chokkalingam AP, Gao YT et al (2002) Allium vegetables and risk of prostate cancer: a population-based study. J Natl Cancer Inst 94:1648–1651

    PubMed  CAS  Google Scholar 

  • Ide N, Lau BH (2001) Garlic compounds minimize intracellular oxidative stress and inhibit nuclear factor-kappa B activation. J Nutr 131:1020S–1026S

    PubMed  CAS  Google Scholar 

  • Jacob C (2006) A scent of therapy: pharmacological implications of natural products containing redox-active sulfur atoms. Nat Prod Rep 23:851–863. doi:10.1039/b609523m

    PubMed  CAS  Google Scholar 

  • Jacob C, Anwar A (2008) The chemistry behind redox regulation with a focus on sulphur redox systems. Physiol Plant 133:469–480. doi:10.1111/j.1399-3054.2008.01080.x

    PubMed  CAS  Google Scholar 

  • Jacob C, Giles GI, Giles NM, Sies H (2003) Sulfur and selenium: the role of oxidation state in protein structure and function. Angew Chem Int Ed Engl 42:4742–4758. doi:10.1002/anie.200300573

    PubMed  CAS  Google Scholar 

  • Jacob C, Knight I, Winyard PG (2006) Aspects of the biological redox chemistry of cysteine: from simple redox responses to sophisticated signalling pathways. Biol Chem 387:1385–1397. doi:10.1515/BC.2006.174

    PubMed  CAS  Google Scholar 

  • Jastrzebski Z, Leontowicz H, Leontowicz M et al (2007) The bioactivity of processed garlic (Allium sativum L.) as shown in vitro and in vivo studies on rats. Food Chem Toxicol 45:1626–1633. doi:10.1016/j.fct.2007.02.028

    PubMed  CAS  Google Scholar 

  • Karmakar S, Banik NL, Patel SJ, Ray SK (2007) Garlic compounds induced calpain and intrinsic caspase cascade for apoptosis in human malignant neuroblastoma SH-SY5Y cells. Apoptosis 12:671–684. doi:10.1007/s10495-006-0024-x

    PubMed  CAS  Google Scholar 

  • Kawai Y, Morinaga H, Kondo H et al (2004) Endogenous formation of novel halogenated 2′-deoxycytidine. Hypohalous acid-mediated DNA modification at the site of inflammation. J Biol Chem 279:51241–51249. doi:10.1074/jbc.M408210200

    PubMed  CAS  Google Scholar 

  • Keiss HP, Dirsch VM, Hartung T et al (2003) Garlic (Allium sativum L.) modulates cytokine expression in lipopolysaccharide-activated human blood thereby inhibiting NF-kappaB activity. J Nutr 133:2171–2175

    PubMed  CAS  Google Scholar 

  • Kim YA, Xiao D, Xiao H et al (2007) Mitochondria-mediated apoptosis by diallyl trisulfide in human prostate cancer cells is associated with generation of reactive oxygen species and regulated by Bax/Bak. Mol Cancer Ther 6:1599–1609. doi:10.1158/1535-7163.MCT-06-0754

    PubMed  CAS  Google Scholar 

  • Klaunig JE, Kamendulis LM (2004) The role of oxidative stress in carcinogenesis. Annu Rev Pharmacol Toxicol 44:239–267. doi:10.1146/annurev.pharmtox.44.101802.121851

    PubMed  CAS  Google Scholar 

  • Knowles LM, Milner JA (2000) Allyl sulfides modify cell growth. Drug Metab Drug Interact 17:81–107

    CAS  Google Scholar 

  • Kwon KB, Yoo SJ, Ryu DG et al (2002) Induction of apoptosis by diallyl disulfide through activation of caspase-3 in human leukemia HL-60 cells. Biochem Pharmacol 63:41–47. doi:10.1016/S0006-2952(01)00860-7

    PubMed  CAS  Google Scholar 

  • Lanzotti V (2005) Bioactive saponins from Allium and Aster plants. Phytochem Rev 4:95–110. doi:10.1007/s11101-005-1254-1

    CAS  Google Scholar 

  • Lanzotti V (2006) The analysis of onion and garlic. J Chromatogr A 1112:3–22. doi:10.1016/j.chroma.2005.12.016

    PubMed  CAS  Google Scholar 

  • Laurent A, Nicco C, Chereau C et al (2005) Controlling tumor growth by modulating endogenous production of reactive oxygen species. Cancer Res 65:948–956

    PubMed  CAS  Google Scholar 

  • Lawenda BD, Kelly KM, Ladas EJ, Sagar SM, Vickers A, Blumberg JB (2008) Should supplemental antioxidant administration be avoided during chemotherapy and radiation therapy? J Natl Cancer Inst 100:773–783. doi:10.1093/jnci/djn148

    PubMed  CAS  Google Scholar 

  • Li M, Ciu JR, Ye Y et al (2002a) Antitumor activity of Z-ajoene, a natural compound purified from garlic: antimitotic and microtubule-interaction properties. Carcinogenesis 23:573–579. doi:10.1093/carcin/23.4.573

    PubMed  CAS  Google Scholar 

  • Li M, Min JM, Cui JR et al (2002b) Z-ajoene induces apoptosis of HL-60 cells: involvement of Bcl–2 cleavage. Nutr Cancer 42:241–247. doi:10.1207/S15327914NC422_14

    PubMed  CAS  Google Scholar 

  • Liu HG, Xu LH (2007) Garlic oil prevents tributyltin-induced oxidative damage in vivo and in vitro. J Food Prot 70:716–721

    PubMed  CAS  Google Scholar 

  • Liu KL, Chen HW, Wang RY, Lei YP, Sheen LY, Lii CK (2006) DATS reduces LPS-induced iNOS expression, NO production, oxidative stress, and NF-kappaB activation in RAW 264.7 macrophages. J Agric Food Chem 54:3472–3478. doi:10.1021/jf060043k

    PubMed  CAS  Google Scholar 

  • Loft S, Poulsen HE (1996) Cancer risk and oxidative DNA damage in man. J Mol Med 74:297–312. doi:10.1007/BF00207507

    PubMed  CAS  Google Scholar 

  • Lu HF, Sue CC, Yu CS, Chen SC, Chen GW, Chung JG (2004) Diallyl disulfide (DADS) induced apoptosis undergo caspase-3 activity in human bladder cancer T24 cells. Food Chem Toxicol 42:1543–1552. doi:10.1016/j.fct.2003.06.001

    PubMed  CAS  Google Scholar 

  • McCord JM (1998) Oxidative stress in cancer, aids, and neurogenerative diseases. Marcel Dekker, Inc., Paris

  • McCord JM (2002) Oxidative stress related diseases—overview. In: Rodriguez H, Cutler R (eds) Oxidative stress and aging: advances in basic science, diagnostics, and intervention. World Scientific Publishing Co., Singapore

    Google Scholar 

  • McFadyen MC, Melvin WT, Murray GI (2004) Cytochrome P450 enzymes: novel options for cancer therapeutics. Mol Cancer Ther 3:363–371

    PubMed  CAS  Google Scholar 

  • Miron T, Rabinkov A, Mirelman D, Wilchek M, Weiner L (2000) The mode of action of allicin: its ready permeability through phospholipid membranes may contribute to its biological activity. Biochim Biophys Acta 1463:20–30. doi:10.1016/S0005-2736(99)00174-1

    PubMed  CAS  Google Scholar 

  • Moeller BJ, Cao Y, Li CY, Dewhirst MW (2004) Radiation activates HIF-1 to regulate vascular radiosensitivity in tumors: role of reoxygenation, free radicals, and stress granules. Cancer Cell 5:429–441. doi:10.1016/S1535-6108(04)00115-1

    PubMed  CAS  Google Scholar 

  • Munchberg U, Anwar A, Mecklenburg S, Jacob C (2007) Polysulfides as biologically active ingredients of garlic. Org Biomol Chem 5:1505–1518. doi:10.1039/b703832a

    PubMed  Google Scholar 

  • Munday R, Munday JS, Munday CM (2003) Comparative effects of mono-, di-, tri-, and tetrasulfides derived from plants of the Allium family: redox cycling in vitro and hemolytic activity and Phase 2 enzyme induction in vivo. Free Radic Biol Med 34:1200–1211. doi:10.1016/S0891-5849(03)00144-8

    PubMed  CAS  Google Scholar 

  • Murugavel P, Pari L (2007a) Diallyl tetrasulfide modulates the cadmium-induced impairment of membrane bound enzymes in rats. J Basic Clin Physiol Pharmacol 18:37–48

    PubMed  CAS  Google Scholar 

  • Murugavel P, Pari L (2007b) Effects of diallyl tetrasulfide on cadmium-induced oxidative damage in the liver of rats. Hum Exp Toxicol 26:527–534. doi:10.1177/0960327107073810

    PubMed  CAS  Google Scholar 

  • Mytar B, Siedlar M, Woloszyn M, Ruggiero I, Pryjma J, Zembala M (1999) Induction of reactive oxygen intermediates in human monocytes by tumour cells and their role in spontaneous monocyte cytotoxicity. Br J Cancer 79:737–743. doi:10.1038/sj.bjc.6690118

    PubMed  CAS  Google Scholar 

  • NCI (2008) Garlic and Cancer Prevention

  • Ngo SN, Williams DB, Cobiac L, Head RJ (2007) Does garlic reduce risk of colorectal cancer? A systematic review. J Nutr 137:2264–2269

    PubMed  CAS  Google Scholar 

  • Nishikawa M (2008) Reactive oxygen species in tumor metastasis. Cancer Lett 266:53–59. doi:10.1016/j.canlet.2008.02.031

    PubMed  CAS  Google Scholar 

  • Nishimura H, Higuchi O, Tateshita K, Tomobe K, Okuma Y, Nomura Y (2006) Antioxidative activity and ameliorative effects of memory impairment of sulfur-containing compounds in Allium species. Biofactors 26:135–146. doi:10.1002/biof.5520260204

    PubMed  CAS  Google Scholar 

  • Oommen S, Anto RJ, Srinivas G, Karunagaran D (2004) Allicin (from garlic) induces caspase-mediated apoptosis in cancer cells. Eur J Pharmacol 485:97–103. doi:10.1016/j.ejphar.2003.11.059

    PubMed  CAS  Google Scholar 

  • Panayiotidis M (2008) Reactive oxygen species (ROS) in multistage carcinogenesis. Cancer Lett 266:3–5. doi:10.1016/j.canlet.2008.02.027

    PubMed  CAS  Google Scholar 

  • Park EK, Kwon KB, Park KI, Park BH, Jhee EC (2002a) Role of Ca(2+) in diallyl disulfide-induced apoptotic cell death of HCT-15 cells. Exp Mol Med 34:250–257

    PubMed  CAS  Google Scholar 

  • Park KA, Kweon S, Choi H (2002b) Anticarcinogenic effect and modification of cytochrome P450 2E1 by dietary garlic powder in diethylnitrosamine-initiated rat hepatocarcinogenesis. J Biochem Mol Biol 35:615–622

    PubMed  CAS  Google Scholar 

  • Park SY, Cho SJ, Kwon HC, Lee KR, Rhee DK, Pyo S (2005) Caspase-independent cell death by allicin in human epithelial carcinoma cells: involvement of PKA. Cancer Lett 224:123–132

    PubMed  CAS  Google Scholar 

  • Patya M, Zahalka MA, Vanichkin A et al (2004) Allicin stimulates lymphocytes and elicits an antitumor effect: a possible role of p21ras. Int Immunol 16:275–281. doi:10.1093/intimm/dxh038

    PubMed  CAS  Google Scholar 

  • Pelicano H, Carney D, Huang P (2004) ROS stress in cancer cells and therapeutic implications. Drug Resist Updat 7:97–110. doi:10.1016/j.drup.2004.01.004

    PubMed  CAS  Google Scholar 

  • Prasad KN, Kumar A, Kochupillai V, Cole WC (1999) High doses of multiple antioxidant vitamins: essential ingredients in improving the efficacy of standard cancer therapy. J Am Coll Nutr 18:13–25

    PubMed  CAS  Google Scholar 

  • Prasad S, Kalra N, Srivastava S, Shukla Y (2008) Regulation of oxidative stress-mediated apoptosis by diallyl sulfide in DMBA-exposed Swiss mice. Hum Exp Toxicol 27:55–63. doi:10.1177/0960327108088978

    PubMed  CAS  Google Scholar 

  • Ratnam DV, Ankola DD, Bhardwaj V, Sahana DK, Kumar MN (2006) Role of antioxidants in prophylaxis and therapy: a pharmaceutical perspective. J Control Release 113:189–207. doi:10.1016/j.jconrel.2006.04.015

    PubMed  CAS  Google Scholar 

  • Robert V, Mouille B, Mayeur C, Michaud M, Blachier F (2001) Effects of the garlic compound diallyl disulfide on the metabolism, adherence and cell cycle of HT-29 colon carcinoma cells: evidence of sensitive and resistant sub-populations. Carcinogenesis 22:1155–1161. doi:10.1093/carcin/22.8.1155

    PubMed  CAS  Google Scholar 

  • Sankaranarayanan A, Narender T, Kumar S, Dikshit M (2007) Allium sativum constituents: effect on free radical generation from rat neutrophils. Cell Mol Biol (Noisy-le-grand) 53:63–67

    CAS  Google Scholar 

  • Seki T, Tsuji K, Hayato Y, Moritomo T, Ariga T (2000) Garlic and onion oils inhibit proliferation and induce differentiation of HL-60 cells. Cancer Lett 160:29–35. doi:10.1016/S0304-3835(00)00552-8

    PubMed  CAS  Google Scholar 

  • Serrano J, Palmeira CM, Kuehl DW, Wallace KB (1999) Cardioselective and cumulative oxidation of mitochondrial DNA following subchronic doxorubicin administration. Biochim Biophys Acta 1411:201–205. doi:10.1016/S0005-2728(99)00011-0

    PubMed  CAS  Google Scholar 

  • Setiawan VW, Yu GP, Lu QY et al (2005) Allium vegetables and stomach cancer risk in China. Asian Pac J Cancer Prev 6:387–395

    PubMed  Google Scholar 

  • Sheweita SA, Abd El-Gabar M, Bastawy M (2001) Carbon tetrachloride-induced changes in the activity of phase II drug-metabolizing enzyme in the liver of male rats: role of antioxidants. Toxicology 165:217–224. doi:10.1016/S0300-483X(01)00429-2

    PubMed  CAS  Google Scholar 

  • Shukla Y, Kalra N (2007) Cancer chemoprevention with garlic and its constituents. Cancer Lett 247:167–181. doi:10.1016/j.canlet.2006.05.009

    PubMed  CAS  Google Scholar 

  • Siegers CP, Robke A, Pentz R (1999) Effects of garlic preparations on superoxide production by phorbol ester activated granulocytes. Phytomedicine 6:13–16

    PubMed  CAS  Google Scholar 

  • Sies H (1985) Oxidative stress: introductory remarks. In: Sies H (ed) Oxidative stress. Academic Press, pp 1–8

    Google Scholar 

  • Sigounas G, Hooker J, Anagnostou A, Steiner M (1997a) S-allylmercaptocysteine inhibits cell proliferation and reduces the viability of erythroleukemia, breast, and prostate cancer cell lines. Nutr Cancer 27:186–191

    PubMed  CAS  Google Scholar 

  • Sigounas G, Hooker JL, Li W, Anagnostou A, Steiner M (1997b) S-allylmercaptocysteine, a stable thioallyl compound, induces apoptosis in erythroleukemia cell lines. Nutr Cancer 28:153–159

    Article  PubMed  CAS  Google Scholar 

  • Singh SV (2001) Impact of garlic organosulfides on p21(H-ras) processing. J Nutr 131:1046S–1048S

    PubMed  CAS  Google Scholar 

  • Singh SV, Mohan RR, Agarwal R et al (1996) Novel anti-carcinogenic activity of an organosulfide from garlic: inhibition of H-RAS oncogene transformed tumor growth in vivo by diallyl disulfide is associated with inhibition of p21H-ras processing. Biochem Biophys Res Commun 225:660–665. doi:10.1006/bbrc.1996.1226

    PubMed  CAS  Google Scholar 

  • Son EW, Mo SJ, Rhee DK, Pyo S (2006) Inhibition of ICAM-1 expression by garlic component, allicin, in gamma-irradiated human vascular endothelial cells via downregulation of the JNK signaling pathway. Int Immunopharmacol 6:1788–1795. doi:10.1016/j.intimp.2006.07.021

    PubMed  CAS  Google Scholar 

  • Sriram N, Kalayarasan S, Ashokkumar P, Sureshkumar A, Sudhandiran G (2008) Diallyl sulfide induces apoptosis in Colo 320 DM human colon cancer cells: involvement of caspase-3, NF-kappaB, and ERK-2. Mol Cell Biochem 311:157–165. doi:10.1007/s11010-008-9706-8

    PubMed  CAS  Google Scholar 

  • Steinmetz KA, Kushi LH, Bostick RM, Folsom AR, Potter JD (1994) Vegetables, fruit, and colon cancer in the Iowa Women’s Health Study. Am J Epidemiol 139:1–15

    PubMed  CAS  Google Scholar 

  • Sundaresan S, Subramanian P (2008) Prevention of N-nitrosodiethylamine-induced hepatocarcinogenesis by S-allylcysteine. Mol Cell Biochem 310:209–214. doi:10.1007/s11010-007-9682-4

    PubMed  CAS  Google Scholar 

  • Szatrowski TP, Nathan CF (1991) Production of large amounts of hydrogen peroxide by human tumor cells. Cancer Res 51:794–798

    PubMed  CAS  Google Scholar 

  • Takahashi M, Niki E (1998) The effect of oxidative stress on cells by oxygen radicals and its inhibition by antioxidants. In: Montagnier L, Olivier R, Pasquier C (eds) Oxidative stress in cancer, aids and neurogenerative diseases. Marcel Dekker, Tokyo

    Google Scholar 

  • Tanaka S, Haruma K, Kunihiro M et al (2004) Effects of aged garlic extract (AGE) on colorectal adenomas: a double-blinded study. Hiroshima J Med Sci 53:39–45

    PubMed  CAS  Google Scholar 

  • Tapiero H, Townsend DM, Tew KD (2004) Organosulfur compounds from Alliaceae in the prevention of human pathologies. Biomed Pharmacother 58:183–193. doi:10.1016/j.biopha.2004.01.004

    PubMed  CAS  Google Scholar 

  • Thomas M, Zhang P, Noordine ML, Vaugelade P, Chaumontet C, Duee PH (2002) Diallyl disulfide increases rat H-ferritin, L-ferritin and transferrin receptor genes in vitro in hepatic cells and in vivo in liver. J Nutr 132:3638–3641

    PubMed  CAS  Google Scholar 

  • Tilli CM, Stavast-Kooy AJ, Vuerstaek JD et al (2003) The garlic-derived organosulfur component ajoene decreases basal cell carcinoma tumor size by inducing apoptosis. Arch Dermatol Res 295:117–123. doi:10.1007/s00403-003-0404-9

    PubMed  CAS  Google Scholar 

  • Tsai CW, Chen HW, Yang JJ, Sheen LY, Lii CK (2007) Diallyl disulfide and diallyl trisulfide up-regulate the expression of the pi class of glutathione S-transferase via an AP-1-dependent pathway. J Agric Food Chem 55:1019–1026. doi:10.1021/jf061874t

    PubMed  CAS  Google Scholar 

  • Ushio-Fukai M, Nakamura Y (2008) Reactive oxygen species and angiogenesis: NADPH oxidase as target for cancer therapy. Cancer Lett 266:37–52. doi:10.1016/j.canlet.2008.02.044

    PubMed  CAS  Google Scholar 

  • Wen J, Zhang Y, Chen X, Shen L, Li GC, Xu M (2004) Enhancement of diallyl disulfide-induced apoptosis by inhibitors of MAPKs in human HepG2 hepatoma cells. Biochem Pharmacol 68:323–331. doi:10.1016/j.bcp.2004.03.027

    PubMed  CAS  Google Scholar 

  • Wiese AG, Pacifici RE, Davies KJ (1995) Transient adaptation of oxidative stress in mammalian cells. Arch Biochem Biophys 318:231–240. doi:10.1006/abbi.1995.1225

    PubMed  CAS  Google Scholar 

  • Winyard PG, Moody CJ, Jacob C (2005) Oxidative activation of antioxidant defence. Trends Biochem Sci 30:453–461. doi:10.1016/j.tibs.2005.06.001

    PubMed  CAS  Google Scholar 

  • Wu CC, Sheen LY, Chen HW, Kuo WW, Tsai SJ, Lii CK (2002) Differential effects of garlic oil and its three major organosulfur components on the hepatic detoxification system in rats. J Agric Food Chem 50:378–383. doi:10.1021/jf010937z

    PubMed  CAS  Google Scholar 

  • Wu CC, Chung JG, Tsai SJ, Yang JH, Sheen LY (2004) Differential effects of allyl sulfides from garlic essential oil on cell cycle regulation in human liver tumor cells. Food Chem Toxicol 42:1937–1947. doi:10.1016/j.fct.2004.07.008

    PubMed  CAS  Google Scholar 

  • Wu X, Kassie F, Mersch-Sundermann V (2005) Induction of apoptosis in tumor cells by naturally occurring sulfur-containing compounds. Mutat Res 589:81–102. doi:10.1016/j.mrrev.2004.11.001

    PubMed  CAS  Google Scholar 

  • Xiao D, Singh SV (2006) Diallyl trisulfide, a constituent of processed garlic, inactivates Akt to trigger mitochondrial translocation of BAD and caspase-mediated apoptosis in human prostate cancer cells. Carcinogenesis 27:533–540. doi:10.1093/carcin/bgi228

    PubMed  CAS  Google Scholar 

  • Xiao D, Pinto JT, Soh JW et al (2003) Induction of apoptosis by the garlic-derived compound S-allylmercaptocysteine (SAMC) is associated with microtubule depolymerization and c-Jun NH(2)-terminal kinase 1 activation. Cancer Res 63:6825–6837

    PubMed  CAS  Google Scholar 

  • Xiao D, Choi S, Johnson DE et al (2004) Diallyl trisulfide-induced apoptosis in human prostate cancer cells involves c-Jun N-terminal kinase and extracellular-signal regulated kinase-mediated phosphorylation of Bcl-2. Oncogene 23:5594–5606. doi:10.1038/sj.onc.1207747

    PubMed  CAS  Google Scholar 

  • Xiao D, Pinto JT, Gundersen GG, Weinstein IB (2005a) Effects of a series of organosulfur compounds on mitotic arrest and induction of apoptosis in colon cancer cells. Mol Cancer Ther 4:1388–1398. doi:10.1158/1535-7163.MCT-05-0152

    PubMed  CAS  Google Scholar 

  • Xiao D, Herman-Antosiewicz A, Antosiewicz J et al (2005b) Diallyl trisulfide-induced G(2)-M phase cell cycle arrest in human prostate cancer cells is caused by reactive oxygen species-dependent destruction and hyperphosphorylation of Cdc 25 C. Oncogene 24:6256–6268. doi:10.1038/sj.onc.1208759

    PubMed  CAS  Google Scholar 

  • Xiao D, Li M, Herman-Antosiewicz A et al (2006) Diallyl trisulfide inhibits angiogenic features of human umbilical vein endothelial cells by causing Akt inactivation and down-regulation of VEGF and VEGF-R2. Nutr Cancer 55:94–107. doi:10.1207/s15327914nc5501_12

    PubMed  CAS  Google Scholar 

  • Yang CS, Chhabra SK, Hong JY, Smith TJ (2001) Mechanisms of inhibition of chemical toxicity and carcinogenesis by diallyl sulfide (DAS) and related compounds from garlic. J Nutr 131:1041S–1045S

    PubMed  CAS  Google Scholar 

  • Yin M-C, Cheng W-S (1998) Antioxidant activity of several Allium members. J Agric Food Chem 46:4097–4101. doi:10.1021/jf980344x

    CAS  Google Scholar 

Download references

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.

Author information

Authors and Affiliations

  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

Authors
  1. C. Scherer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C. Jacob
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Dicato
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. Diederich
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M. Diederich.

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11101-009-9122-z

Keywords

Search

Navigation