Advertisement

The Role of Organosulfur Compounds Derived From Allium Vegetables in Cancer Prevention and Therapy

Chapter
  • 811 Downloads

Abstract

Organosulfur compounds (OSCs) are a group of small molecules commonly present in Allium vegetables, such as garlic, onions chives, and shallots that have garnered scientific interest for their noted health benefits. OSCs have been evaluated for their potential to prevent or treat major diseases including cancer. Epidemiological evidence of inverse association between increased intake of Allium vegetables and cancer risk is now substantiated by animal studies wherein true causal relationships between OSCs and cancer prevention have been found. This chapter summarizes the chemistry, metabolism, and bioavailability of commonly studied OSCs and the latest developments regarding their anticarcinogenic effects in cell culture and animal models. Data pertinent to clinical trials assessing safety and anticancer efficacy of OSCs are also discussed.

Keywords

Prostate Cancer Cell Proliferate Cell Nuclear Antigen Reactive Oxygen Species Generation Aberrant Crypt Focus Aristolochic Acid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

5-FU

5-Fluorouracil

AA

Aristolochic acid

ALT

Alanine aminotransferase

AST

Aspartate aminotransferase

B[a]P

Benzo[a]pyrene

CA

Cancer

CCl4

Carbon tetrachloride

COX-2

Cyclooxygenase 2

CYP 2E1

Cytochrome P450 isoenzyme 2E1

DADS

Diallyl disulfide

DAS

Diallyl sulfide

DATS

Diallyl trisulfide

DMBA

7,12-Dimethylbenz[a]anthracene

DMH

Dimethylhydrazine

DR4 and DR5

Death receptor

ERK

Extracellular signal-regulated kinase

GST

Glutathione-S-transferase

HDACs

Histone deacetylases

HMG-CoA

3-Hydroxy-3-methyl-glutaryl-Coenzyme A

HUVEC

Human umbilical vein endothelial cells

i.p.

Intraperitoneal

JNK

c-Jun N-terminal kinases

MNNG

Methylnitronitrosoguanidine

MMP

Matrix metalloprotease

NAC

N-acetyl-l-cysteine

NDEA

N-nitrosodiethylamine

NDMA

N-nitrosodimethylamine

NDN

N-diethylnitrosamine

NMBA

N-nitrosomethylbenzylamine

NF-κB

Nuclear factor-κB

NKK

(methylnitrosamino)1-(3-pyridyl)-1-butanone

NMU

N-methylnitrosourea

OSCs

Organosulfur compounds

PAH

Polycyclic aromatic hydrocarbon

PBS

Phosphate-buffered saline

PCNA

Proliferating cell nuclear antigen

PFE

Pomegranate fruit extract

PK

Pharmacokinetic

ppm

Parts per million

PSA

Prostate-specific antigen

pSTAT3

Phosphorylated signal transducer and activator of transcription 3

q3d

Every 3 days

q4d

Every 4 days

qod

Every other day

qd

Every day

ROS

Reactive Oxygen Species

s.c.

Subcutaneous

SAC

S-allylcysteine

SAMC

S-allylmercaptocysteine

S-NaCl

Saturated sodium chloride

TPA

12-O-tetradecanoylphorbol 13-acetate

TRAIL

Tumor necrosis factor-related apoptosis-inducing ligand

TRAMP

Transgenic adenoma of a mouse prostate

VC

Vinyl carbamate

XIAP

X-linked inhibitor of apoptosis protein

Z-ajoene

Z isomer of ajoene

References

  1. Agarwal KC (1996) Therapeutic actions of garlic constituents. Med Res Rev 16(1):111–124CrossRefGoogle Scholar
  2. Amagase H, Petesch BL, Matsuura H et al (2001) Intake of garlic and its bioactive components. J Nutr 131(3s):955S–962SGoogle Scholar
  3. Antony ML, Singh SV (2011) Molecular mechanisms and targets of cancer chemoprevention by garlic-derived bioactive compound diallyl trisulfide. Indian J Exp Biol 49(11):805–816Google Scholar
  4. 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(10):5379–86CrossRefGoogle Scholar
  5. Aquilano K, Vigilanza P, Filomeni G et al (2010) Tau dephosphorylation and microfilaments disruption are upstream events of the anti-proliferative effects of DADS in SH-SY5Y cells. J Cell Mol Med 14(3):564–577Google Scholar
  6. Bauer D, Mazzio E, Soliman KF et al (2014) Diallyl disulfide inhibits TNFalpha-induced CCL2 release by MDA-MB-231 cells. Anticancer Res 34(6):2763–2770Google Scholar
  7. Benavides GA, Squadrito GL, Mills RW et al (2007) Hydrogen sulfide mediates the vasoactivity of garlic. Proc Natl Acad Sci U S A 104(46):17977–17982CrossRefGoogle Scholar
  8. Bianchini F, Vainio H (2001) Allium vegetables and organosulfur compounds: do they help prevent cancer? Environ Health Perspect 109(9):893–902CrossRefGoogle Scholar
  9. Block E (1992) The organosulfur chemistry of the Genus Allium-Implications for the organochemistry of sulfur. Angew Chemie 31(9):1135–1178CrossRefGoogle Scholar
  10. Block E, Ahmad S, Jain MK et al (1984) The chemistry of alkyl thiosulfate esters. 8. (E, Z)-Ajoene: a potent antithrombotic agent from garlic. J Am Chem Soc 106(26):8295–8296CrossRefGoogle Scholar
  11. Brady JF, Ishizaki H, Fukuto JM et al (1991) Inhibition of cytochrome P-450 2E1 by diallyl sulfide and its metabolites. Chem Res Toxicol 4(6):642–647CrossRefGoogle Scholar
  12. Chandra-Kuntal K, Singh SV (2010) Diallyl trisulfide inhibits activation of signal transducer and activator of transcription 3 in prostate cancer cells in culture and in vivo. Cancer Prev Res (Phila) 3(11):1473–1483CrossRefGoogle Scholar
  13. Chittezhath M, Kuttan G (2006) Radioprotective activity of naturally occurring organosulfur compounds. Tumori 92(2):163–169Google Scholar
  14. Choi YH, Park HS (2012) Apoptosis induction of U937 human leukemia cells by diallyl trisulfide induces through generation of reactive oxygen species. J Biomed Sci 19:50CrossRefGoogle Scholar
  15. Chu Q, Lee DT, Tsao SW et al (2006) S-allylcysteine, a water-soluble garlic derivative, suppresses the growth of a human androgen-independent prostate cancer xenograft, CWR22R, under in vivo conditions. BJU Int 99(4):925–932CrossRefGoogle Scholar
  16. Cohen LA, Zhao Z, Pittman B et al (1999) S-allylcysteine, a garlic constituent, fails to inhibit N-methylnitrosourea-induced rat mammary tumorigenesis. Nutr Cancer 35(1):58–63CrossRefGoogle Scholar
  17. Dasgupta P, Bandyopadhyay SS (2013) Role of di-allyl disulfide, a garlic component in NF-kappaB mediated transient G2-M phase arrest and apoptosis in human leukemic cell-lines. Nutr Cancer 65(4):611–622CrossRefGoogle Scholar
  18. 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 kappaB. Mol Pharmacol 53(3):402–407Google Scholar
  19. 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(7):1227–1236CrossRefGoogle Scholar
  20. Druesne-Pecollo N, Latino-Martel P (2011) Modulation of histone acetylation by garlic sulfur compounds. Anticancer Agents Med Chem 11(3):254–259CrossRefGoogle Scholar
  21. Dwivedi C, Rohlfs S, Jarvis D et al (1992) Chemoprevention of chemically induced skin tumor development by diallyl sulfide and diallyl disulfide. Pharm Res 9(12):1668–1670CrossRefGoogle Scholar
  22. Ebrahimi M, Mohammad Hassan Z, Mostafaie A et al (2013) Purified protein fraction of garlic extract modulates cellular immune response against breast transplanted tumors in BALB/c mice model. Cell J 15(1):65–75Google Scholar
  23. Filomeni G, Aquilano K, Rotilio G et al (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(18):5940–5949Google Scholar
  24. Galeone C, Pelucchi C, Dal Maso L et al (2008) Allium vegetables intake and endometrial cancer risk. Public Health Nutr 12(9):1576–1579CrossRefGoogle Scholar
  25. George J, Singh M, Srivastava AK et al (2011) Synergistic growth inhibition of mouse skin tumors by pomegranate fruit extract and diallyl sulfide: evidence for inhibition of activated MAPKs/NF-kappaB and reduced cell proliferation. Food Chem Toxicol 49(7):1511–1520CrossRefGoogle Scholar
  26. Hadjiolov D, Fernando RC, Schmeiser HH et al (1993) Effect of diallyl sulfide on aristolochic acid-induced forestomach carcinogenesis in rats. Carcinogenesis 14(3):407–410CrossRefGoogle Scholar
  27. Hatono S, Jimenez A, Wargovich MJ (1996) Chemopreventive effect of S-allylcysteine and its relationship to the detoxification enzyme glutathione S-transferase. Carcinogenesis 17(5):1041–1044CrossRefGoogle Scholar
  28. Herman-Antosiewicz A, Singh SV (2005) Checkpoint kinase 1 regulates diallyl trisulfide-induced mitotic arrest in human prostate cancer cells. J Biol Chem 280(31):28519–28528CrossRefGoogle Scholar
  29. Herman-Antosiewicz A, Powolny AA, Singh SV (2007) Molecular targets of cancer chemoprevention by garlic-derived organosulfides. Acta Pharmacol Sin 28(9):1355–1364CrossRefGoogle Scholar
  30. Higdon J (2007) An evidence-based approach to dietary phytochemicals, 1st ed. Thieme PublishersGoogle Scholar
  31. Hong JY, Wang ZY, Smith TJ et al (1992) Inhibitory effects of diallyl sulfide on the metabolism and tumorigenicity of the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in A/J mouse lung. Carcinogenesis 13(5):901–904CrossRefGoogle Scholar
  32. Hong YS, Ham YA, Choi JH et al (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 32:127–134CrossRefGoogle Scholar
  33. 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(50):41487–41493CrossRefGoogle Scholar
  34. Hui C, Jun W, Ya LN et al (2008) Effect of Allium sativum (garlic) diallyl disulfide (DADS) on human non-small cell lung carcinoma H1299 cells. Trop Biomed 25(1):37–45Google Scholar
  35. Ip C, Lisk DJ, Stoewsand GS (1992) Mammary cancer prevention by regular garlic and selenium-enriched garlic. Nutr Cancer 17(3):279–286CrossRefGoogle Scholar
  36. Karmakar S, Banik NL, Patel SJ et al (2007) Garlic compounds induced calpain and intrinsic caspase cascade for apoptosis in human malignant neuroblastoma SH-SY5Y cells. Apoptosis 12(4):671–684CrossRefGoogle Scholar
  37. 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(5):1599–1609CrossRefGoogle Scholar
  38. Kim SH, Bommareddy A, Singh SV (2011) Garlic constituent diallyl trisulfide suppresses x-linked inhibitor of apoptosis protein in prostate cancer cells in culture and in vivo. Cancer Prev Res (Phila) 4(6):897–906CrossRefGoogle Scholar
  39. Kim NH, Lee S, Kang MJ et al (2014) Protective effects of diallyl sulfide against Thioacetamide-induced toxicity: a possible role of cytochrome P450 2E1. Biomol Ther (Seoul) 22(2):149–154CrossRefGoogle Scholar
  40. Knowles LM, Milner JA (2000) Diallyl disulfide inhibits p34(cdc2) kinase activity through changes in complex formation and phosphorylation. Carcinogenesis 21(6):1129–1134CrossRefGoogle Scholar
  41. Knowles LM, Milner JA (2003) Diallyl disulfide induces ERK phosphorylation and alters gene expression profiles in human colon tumor cells. J Nutr 133(9):2901–2906Google Scholar
  42. Kyo E, Uda N, Suzuki A et al (1998) Immunomodulation and antitumor activities of aged garlic extract. Phytomedicine 5(4):259–267CrossRefGoogle Scholar
  43. Lai KC, Hsu SC, Kuo CL et al (2013) Diallyl sulfide, diallyl disulfide, and diallyl trisulfide inhibit migration and invasion in human colon cancer colo 205 cells through the inhibition of matrix metalloproteinase-2, -7, and -9 expressions. Environ Toxicol 28(9):479–488CrossRefGoogle Scholar
  44. Lai KC, Hsu SC, Yang JS et al (2015) Diallyl trisulfide inhibits migration, invasion and angiogenesis of human colon cancer HT-29 cells and umbilical vein endothelial cells, and suppresses murine xenograft tumour growth. J Cell Mol Med 19(2):474–484CrossRefGoogle Scholar
  45. Lea MA, Randolph VM (2001) Induction of histone acetylation in rat liver and hepatoma by organosulfur compounds including diallyl disulfide. Anticancer Res 21(4A):2841–2845Google Scholar
  46. Lea MA, Randolph VM, Patel M (1999) Increased acetylation of histones induced by diallyl disulfide and structurally related molecules. Int J Oncol 15(2):347–352Google Scholar
  47. Lea MA, Randolph VM, Lee JE et al (2001) Induction of histone acetylation in mouse erythroleukemia cells by some organosulfur compounds including allyl isothiocyanate. Int J Cancer 92(6):784–789CrossRefGoogle Scholar
  48. 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(4):573–579CrossRefGoogle Scholar
  49. 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(2):241–247CrossRefGoogle Scholar
  50. Li W, Tian H, Li L et al (2012) Diallyl trisulfide induces apoptosis and inhibits proliferation of A549 cells in vitro and in vivo. Acta Biochim Biophys Sin (Shanghai) 44(7):577–583CrossRefGoogle Scholar
  51. Li Y, Zhang J, Zhang L et al (2013) Diallyl trisulfide inhibits proliferation, invasion and angiogenesis of osteosarcoma cells by switching on suppressor microRNAs and inactivating of Notch-1 signaling. Carcinogenesis 34(7):1601–1610CrossRefGoogle Scholar
  52. Liao QJ, Su J, Zhou XT et al (2007) Inhibitory effect of diallyl disulfide on proliferation of human colon cancer cell line SW480 in nude mice. Ai Zheng 26(8):828–832Google Scholar
  53. Liao QJ, Su J, He J et al (2009) Effect of diallyl disulfide on cell cycle arrest of human colon cancer SW480 cells. Ai Zheng 28(2):138–141Google Scholar
  54. Ling H, Wen L, Ji XX et al (2010) Growth inhibitory effect and Chk1-dependent signaling involved in G2/M arrest on human gastric cancer cells induced by diallyl disulfide. Braz J Med Biol Res 43(3):271–278CrossRefGoogle Scholar
  55. Ma JL, Zhang L, Brown LM et al (2012) Fifteen-year effects of Helicobacter pylori, garlic, and vitamin treatments on gastric cancer incidence and mortality. J Natl Cancer Inst 104(6):488–492CrossRefGoogle Scholar
  56. Meyer K, Ueberham E, Gebhardt R (2004) Influence of organosulphur compounds from garlic on the secretion of matrix metalloproteinases and their inhibitor TIMP-1 by cultured HUVEC cells. Cell Biol Toxicol 20(4):253–260CrossRefGoogle Scholar
  57. Millen AE, Subar AF, Graubard BI et al (2007) Fruit and vegetable intake and prevalence of colorectal adenoma in a cancer screening trial. Am J Clin Nutr 86(6):1754–1764Google Scholar
  58. Milner JA (2001) Mechanisms by which garlic and allyl sulfur compounds suppress carcinogen bioactivation. Garlic and carcinogenesis. Adv Exp Med Biol 492:69–81CrossRefGoogle Scholar
  59. Milner J (2004) Organosulfur-garlic compounds and cancer prevention. In: Bao Y, Fenwick R (eds) Phytochemicals in health and disease. Dekker, New York, pp 163–186CrossRefGoogle Scholar
  60. Mousa AS, Mousa SA (2005) Anti-angiogenesis efficacy of the garlic ingredient alliin and antioxidants: role of nitric oxide and p53. Nutr Cancer 53(1):104–110CrossRefGoogle Scholar
  61. Munday R, Munday CM (2001) Relative activities of organosulfur compounds derived from onions and garlic in increasing tissue activities of quinone reductase and glutathione transferase in rat tissues. Nutr Cancer 40(2):205–210CrossRefGoogle Scholar
  62. Na HK, Kim EH, Choi MA et al (2012) Diallyl trisulfide induces apoptosis in human breast cancer cells through ROS-mediated activation of JNK and AP-1. Biochem Pharmacol 84(10):1241–1250CrossRefGoogle Scholar
  63. Nagae S, Ushijima M, Hatono S et al (1994) Pharmacokinetics of the garlic compound S-allylcysteine. Planta Med 60(3):214–217CrossRefGoogle Scholar
  64. Nakagawa H, Tsuta K, Kiuchi K et al (2001) Growth inhibitory effects of diallyl disulfide on human breast cancer cell lines. Carcinogenesis 22(6):891–897CrossRefGoogle Scholar
  65. Ng KT, Guo DY, Cheng Q et al (2012) A garlic derivative, S-allylcysteine (SAC), suppresses proliferation and metastasis of hepatocellular carcinoma. PLoS One 7(2), e31655CrossRefGoogle Scholar
  66. Nishikawa T, Yamada N, Hattori A et al (2002) Inhibition by ajoene of skin-tumor promotion in mice. Biosci Biotechnol Biochem 66(10):2221–2223CrossRefGoogle Scholar
  67. Pai MH, Kuo YH, Chiang EP et al (2012) S-Allylcysteine inhibits tumour progression and the epithelial-mesenchymal transition in a mouse xenograft model of oral cancer. Br J Nutr 108(1):28–38CrossRefGoogle Scholar
  68. Park EK, Kwon KB, Park KI et al (2002) Role of Ca(2+) in diallyl disulfide-induced apoptotic cell death of HCT-15 cells. Exp Mol Med 34(3):250–257CrossRefGoogle Scholar
  69. Powolny AA, Singh SV, Melov S, Hubbard A, Fisher AL (2011) The garlic constituent diallyl trisulfide increases the lifespan of C. elegans via skn-1 activation. Exp Gerontol 46(6):441–52CrossRefGoogle Scholar
  70. Rahman K (2001) Historical perspective on garlic and cardiovascular disease. J Nutr 131(3s):977S–979SGoogle Scholar
  71. Salem S, Salahi M, Mohseni M et al (2011) Major dietary factors and prostate cancer risk: a prospective multicenter case–control study. Nutr Cancer 63(1):21–27Google Scholar
  72. Schafer G, Kaschula CH (2014) The immunomodulation and anti-inflammatory effects of garlic organosulfur compounds in cancer chemoprevention. Anticancer Agents Med Chem 14(2):233–240CrossRefGoogle Scholar
  73. Schulz M, Lahmann PH, Boeing H et al (2005) Fruit and vegetable consumption and risk of epithelial ovarian cancer: the European Prospective Investigation into Cancer and Nutrition. Cancer Epidemiol Biomarkers Prev 14(11 Pt 1):2531–2535CrossRefGoogle Scholar
  74. Shankar S, Chen Q, Ganapathy S et al (2008) Diallyl trisulfide increases the effectiveness of TRAIL and inhibits prostate cancer growth in an orthotopic model: molecular mechanisms. Mol Cancer Ther 7(8):2328–2338CrossRefGoogle Scholar
  75. Shin DY, Kim GY, Kim JI et al (2010) Anti-invasive activity of diallyl disulfide through tightening of tight junctions and inhibition of matrix metalloproteinase activities in LNCaP prostate cancer cells. Toxicol In Vitro 24:1569–1576CrossRefGoogle Scholar
  76. Shrotriya S, Kundu JK, Na HK et al (2010) Diallyl trisulfide inhibits phorbol ester-induced tumor promotion, activation of AP-1, and expression of COX-2 in mouse skin by blocking JNK and Akt signaling. Cancer Res 70(5):1932–1940CrossRefGoogle Scholar
  77. Shukla Y, Kalra N (2007) Cancer chemoprevention with garlic and its constituents. Cancer Lett 247(2):167–181CrossRefGoogle Scholar
  78. Singh A, Shukla Y (1998a) Antitumor activity of diallyl sulfide in two-stage mouse skin model of carcinogenesis. Biomed Environ Sci 11(3):258–263Google Scholar
  79. Singh A, Shukla Y (1998b) Antitumour activity of diallyl sulfide on polycyclic aromatic hydrocarbon-induced mouse skin carcinogenesis. Cancer Lett 131(2):209–214CrossRefGoogle Scholar
  80. 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(2):660–665CrossRefGoogle Scholar
  81. Singh SV, Pan SS, Srivastava SK et al (1998) Differential induction of NAD(P)H:quinone oxidoreductase by anti-carcinogenic organosulfides from garlic. Biochem Biophys Res Commun 244(3):917–920CrossRefGoogle Scholar
  82. Singh SV, Powolny AA, Stan SD et al (2008) Garlic constituent diallyl trisulfide prevents development of poorly differentiated prostate cancer and pulmonary metastasis multiplicity in TRAMP mice. Cancer Res 68(22):9503–9511CrossRefGoogle Scholar
  83. Song JD, Lee SK, Kim KM et al (2009) Molecular mechanism of diallyl disulfide in cell cycle arrest and apoptosis in HCT-116 colon cancer cells. J Biochem Mol Toxicol 23(1):71–79CrossRefGoogle Scholar
  84. Stan SD, Singh SV (2009) Transcriptional repression and inhibition of nuclear translocation of androgen receptor by diallyl trisulfide in human prostate cancer cells. Clin Cancer Res 15(15):4895–4903CrossRefGoogle Scholar
  85. Sundaram SG, Milner JA (1996a) Diallyl disulfide induces apoptosis of human colon tumor cells. Carcinogenesis 17(4):669–673CrossRefGoogle Scholar
  86. Sundaram SG, Milner JA (1996b) Diallyl disulfide suppresses the growth of human colon tumor cell xenografts in athymic nude mice. J Nutr 126(5):1355–1361Google Scholar
  87. Sundaresan S, Subramanian P (2003) S-allylcysteine inhibits circulatory lipid peroxidation and promotes antioxidants in N-nitrosodiethylamine-induced carcinogenesis. Pol J Pharmacol 55(1):37–42Google Scholar
  88. Sundaresan S, Subramanian P (2008) Prevention of N-nitrosodiethylamine-induced hepatocarcinogenesis by S-allylcysteine. Mol Cell Biochem 310(1-2):209–214CrossRefGoogle Scholar
  89. Surh YJ, Lee RC, Park KK et al (1995) Chemoprotective effects of capsaicin and diallyl sulfide against mutagenesis or tumorigenesis by vinyl carbamate and N-nitrosodimethylamine. Carcinogenesis 16(10):2467–2471CrossRefGoogle Scholar
  90. Suzui N, Sugie S, Rahman KM et al (1997) Inhibitory effects of diallyl disulfide or aspirin on 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine-induced mammary carcinogenesis in rats. Jpn J Cancer Res 88(8):705–711CrossRefGoogle Scholar
  91. Takahashi S, Hakoi K, Yada H et al (1992) Enhancing effects of diallyl sulfide on hepatocarcinogenesis and inhibitory actions of the related diallyl disulfide on colon and renal carcinogenesis in rats. Carcinogenesis 13(9):1513–1518CrossRefGoogle Scholar
  92. Tanaka S, Haruma K, Yoshihara M et al (2006) Aged garlic extract has potential suppressive effect on colorectal adenomas in humans. J Nutr 136(3 Suppl):821S–826SGoogle Scholar
  93. Tang H, Kong Y, Guo J et al (2013) Diallyl disulfide suppresses proliferation and induces apoptosis in human gastric cancer through Wnt-1 signaling pathway by up-regulation of miR-200b and miR-22. Cancer Lett 340(1):72–81CrossRefGoogle Scholar
  94. Taylor P, Noriega R, Farah C et al (2006) Ajoene inhibits both primary tumor growth and metastasis of B16/BL6 melanoma cells in C57BL/6 mice. Cancer Lett 239(2):298–304CrossRefGoogle Scholar
  95. Tsai CW, Liu KL, Lin CY et al (2011) Structure and function relationship study of Allium organosulfur compounds on upregulating the pi class of glutathione S-transferase expression. J Agric Food Chem 59(7):3398–3405CrossRefGoogle Scholar
  96. Tsubura A, Lai YC, Kuwata M et al (2011) Anticancer effects of garlic and garlic-derived compounds for breast cancer control. Anticancer Agents Med Chem 11(3):249–253CrossRefGoogle Scholar
  97. Velmurugan B, Bhuvaneswari V, Nagini S (2003) Effect of S-allylcysteine on oxidant-antioxidant status during N-methyl-N'-nitro-N-nitrosoguanidine and saturated sodium chloride-induced gastric carcinogenesis in Wistar rats. Asia Pac J Clin Nutr 12(4):488–494Google Scholar
  98. Velmurugan B, Mani A, Nagini S (2005) Combination of S-allylcysteine and lycopene induces apoptosis by modulating Bcl-2, Bax, Bim and caspases during experimental gastric carcinogenesis. Eur J Cancer Prev 14(4):387–393CrossRefGoogle Scholar
  99. Wallace GC, Haar CP, Vandergrift WA 3rd et al (2013) Multi-targeted DATS prevents tumor progression and promotes apoptosis in ectopic glioblastoma xenografts in SCID mice via HDAC inhibition. J Neurooncol 114(1):43–50CrossRefGoogle Scholar
  100. Wang EJ, Li Y, Lin M et al (1996) Protective effects of garlic and related organosulfur compounds on acetaminophen-induced hepatotoxicity in mice. Toxicol Appl Pharmacol 136(1):146–154CrossRefGoogle Scholar
  101. Wang HC, Yang JH, Hsieh SC et al (2010) Allyl sulfides inhibit cell growth of skin cancer cells through induction of DNA damage mediated G2/M arrest and apoptosis. J Agric Food Chem 58(11):7096–7103CrossRefGoogle Scholar
  102. Wang HC, Hsieh SC, Yang JH et al (2012a) Diallyl trisulfide induces apoptosis of human basal cell carcinoma cells via endoplasmic reticulum stress and the mitochondrial pathway. Nutr Cancer 64(5):770–780CrossRefGoogle Scholar
  103. Wang Q, Wang Y, Ji Z et al (2012b) Risk factors for multiple myeloma: a hospital-based case–control study in Northwest China. Cancer Epidemiol 36(5):439–444CrossRefGoogle Scholar
  104. Wargovich MJ, Woods C, Eng VW et al (1988) Chemoprevention of N-nitrosomethylbenzylamine-induced esophageal cancer in rats by the naturally occurring thioether, diallyl sulfide. Cancer Res 48(23):6872–6875Google Scholar
  105. Wargovich MJ, Imada O, Stephens LC (1992) Initiation and post-initiation chemopreventive effects of diallyl sulfide in esophageal carcinogenesis. Cancer Lett 64(1):39–42CrossRefGoogle Scholar
  106. Wu CC, Chung JG, Tsai SJ et al (2004) Differential effects of allyl sulfides from garlic essential oil on cell cycle regulation in human liver tumor cells. Food Chem Toxicol 42:1937–1947CrossRefGoogle Scholar
  107. Wu XJ, Hu Y, Lamy E, Mersch-Sundermann V (2009) Apoptosis induction in human lung adenocarcinoma cells by oil-soluble allyl sulfides: triggers, pathways, and modulators. Environ Mol Mutagen 50(3):266–275Google Scholar
  108. Wu PP, Liu KC, Huang WW et al (2011) Diallyl trisulfide (DATS) inhibits mouse colon tumor in mouse CT-26 cells allograft model in vivo. Phytomedicine 18(8-9):672–676CrossRefGoogle Scholar
  109. Xiang SL, Xiao XL, Ling H et al (2005) Antitumor effect of diallyl disulfide on human gastric cancer MGC803 cells xenograft in nude mice. Ai Zheng 24(8):940–944Google Scholar
  110. 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(33):5594–5606CrossRefGoogle Scholar
  111. Xiao D, Herman-Antosiewicz A, Antosiewicz J et al (2005) 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(41):6256–6268CrossRefGoogle Scholar
  112. Xiao D, Lew KL, Kim YA et al (2006a) Diallyl trisulfide suppresses growth of PC-3 human prostate cancer xenograft in vivo in association with Bax and Bak induction. Clin Cancer Res 12(22):6836–6843CrossRefGoogle Scholar
  113. Xiao D, Li M, Herman-Antosiewicz A et al (2006b) 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(1):94–107CrossRefGoogle Scholar
  114. Yang JS, Kok LF, Lin YH et al (2006) Diallyl disulfide inhibits WEHI-3 leukemia cells in vivo. Anticancer Res 26(1A):219–225Google Scholar
  115. Zhang ZM, Yang XY, Deng SH et al (2007) Anti-tumor effects of polybutylcyanoacrylate nanoparticles of diallyl trisulfide on orthotopic transplantation tumor model of hepatocellular carcinoma in BALB/c nude mice. Chin Med J (Engl) 120(15):1336–1342Google Scholar
  116. Zhang W, Xiang YB, Li HL et al (2013) Vegetable-based dietary pattern and liver cancer risk: results from the Shanghai women's and men's health studies. Cancer Sci 104(10):1353–1361CrossRefGoogle Scholar
  117. Yi L, Su Q (2013) Molecular mechanisms for the anti-cancer effects of diallyl disulfide. Food Chem Toxicol 57:362–370CrossRefGoogle Scholar
  118. Yuan JP, Wang GH, Ling H et al (2004) Diallyl disulfide-induced G2/M arrest of human gastric cancer MGC803 cells involves activation of p38 MAP kinase pathways. World J Gastroenterol 10(18):2731–2734CrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Department of Pharmaceutical Sciences, Nesbitt School of PharmacyWilkes UniversityWilkes-BarreUSA
  2. 2.Department of Pharmacology and Chemical BiologyUniversity of Pittsburgh Cancer Institute, University of Pittsburgh School of MedicinePittsburghUSA

Personalised recommendations