Potential Anticancer Effects of Aged Garlic Extract and its Water-soluble Organosulfur Compounds

Main Article Content

Huda Mohammed Alkreathy


Background: Cancer is among the leading causes of morbidity and mortality globally; it often leads to a steep rise in healthcare expenses. It is a known fact that various dietary ingredients such as aged garlic is an active anticancer agent, and its extracts do not have a strong odor and pungent taste.

Purpose: This review summarizes the potential beneficial effects of aged garlic extract (AGE) and its water-soluble organosulfur compounds on the cancer incidences, and in the prevention and improvement of malignancy factors.

Methods: The study utilizes systematic reviews on publications of previous studies obtained from scholarly journal databases including PubMed, Medline, Ebsco Host, Google Scholar and Cochrane. The study utilizes secondary information based on the studies conducted in cancer cell lines, animal and humans as there are increasing evidence of the efficacy of AGE and AGE-derived water-soluble organosulfur compounds in cancer and other malignancies.

Conclusion and Recommendation: Although animal and laboratory results were mostly consistent, there is variable evidence from human studies. The overall findings suggest that consumption of AGE and AGE-derived organosulfur compounds can offer significant protection against cancer. In our review, we found that there are shortcomings in various studies. Therefore, we recommend that more investigations are necessary to establish whether aged garlic extract could be considered for cancer prevention.


Garlic, organosuphur, cancer, tumour, malignancy, anticancer

Article Details

How to Cite
Alkreathy, H. M. (2020). Potential Anticancer Effects of Aged Garlic Extract and its Water-soluble Organosulfur Compounds. Journal of Pharmaceutical Research International, 32(12), 108-121. https://doi.org/10.9734/jpri/2020/v32i1230568
Review Article


Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394-424.

Paul C, Boyes A, Hall A, Bisquera A, Miller A, O'Brien L. The impact of cancer diagnosis and treatment on employment, income, treatment decisions and financial assistance and their relationship to socioeconomic and disease factors. Support Care Cancer. 2016;24(11):4739-46.

Teng AM, Atkinson J, Disney G, Wilson N, Blakely T. Changing socioeconomic inequalities in cancer incidence and mortality: Cohort study with 54 million person-years follow-up 1981-2011. Int J Cancer. 2017;140(6):1306-16.
DOI: 10.1002/ijc.30555

Block E. The chemistry of garlic and onions. Sci Am. 1985;252(3):114-9.
DOI: 10.1038/scientificamerican0385-114

Ali M, Thomson M, Afzal M. Garlic and onions: their effect on eicosanoid metabolism and its clinical relevance. Prostaglandins Leukot Essent Fatty Acids. 2000;62(2):55-73.
DOI: 10.1054/plef.1999.0124

6. Dolara P, Bigagli E, Collins A. Antioxidant vitamins and mineral supplementation, life span expansion and cancer incidence: a critical commentary. Eur J Nutr. 2012;51(7):769-81.
DOI: 10.1007/s00394-012-0389-2

7. Singh VK, Singh DK. Pharmacological effects of garlic (Allium sativum L.). Annual Review of Biomedical Sciences. 2008;10(1).

Fleischauer AT, Arab L. Garlic and cancer: a critical review of the epidemiologic literature. J Nutr. 2001;131(3s):1032S-40S.
DOI: 10.1093/jn/131.3.1032S

Milner JA. A historical perspective on garlic and cancer. J Nutr. 2001;131(3s):1027S-31S.
DOI: 10.1093/jn/131.3.1027S

Reeve VE, Bosnic M, Rozinova E, Boehm-Wilcox C. A garlic extract protects from ultraviolet B (280-320 nm) radiation-induced suppression of contact hypersensitivity. Photochem Photobiol. 1993;58(6):813-7.
DOI: 10.1111/j.1751-1097.1993.tb04975.x

Wei Z, Lau BHS. Garlic inhibits free radical generation and augments antioxidant enzyme activity in vascular endothelial cells. Nutr Res. 1998;18(1):61-70.

Youn HS, Lim HJ, Lee HJ, Hwang D, Yang M, Jeon R, et al. Garlic (Allium sativum) extract inhibits lipopolysaccharide-induced Toll-like receptor 4 dimerization. Biosci Biotechnol Biochem. 2008;72(2):368-75.
DOI: 10.1271/bbb.70434.

Butt MS, Sultan MT, Butt MS, Iqbal J. Garlic: Nature's protection against physio-logical threats. Crit Rev Food Sci Nutr. 2009;49(6):538-51.
DOI: 10.1080/10408390802145344.

Amagase H. Clarifying the real bioactive constituents of garlic. J Nutr. 2006;136(3 Suppl):716S-25S.
DOI: 10.1093/jn/136.3.716S.

Santhosha SG, Jamuna P, Prabhavathi SN. Bioactive components of garlic and their physiological role in health maintenance: A review. Food Biosci. 2013;3:59-74.

Corzo-Martínez M, Corzo N, Villamiel M. Biological properties of onions and garlic. Trends Food Sci Technol. 2007;18(12): 609-25.

Amagase H, Petesch BL, Matsuura H, Kasuga S, Itakura Y. Intake of garlic and its bioactive components. J Nutr. 2001;131(3s):955S-62S.
DOI: 10.1093/jn/131.3.955S.

Colin-Gonzalez AL, Ali SF, Tunez I, Santamaria A. On the antioxidant, neuroprotective and anti-inflammatory properties of S-allyl cysteine: An update. Neurochem Int. 2015;89:83-91.
DOI: 10.1016/j.neuint.2015.06.011.

Choi IS, Cha HS, Lee YS. Physicochemical and antioxidant properties of black garlic. Molecules. 2014;19(10):16811-23.
DOI: 10.3390/molecules191016811

Nagae S, Ushijima M, Hatono S, Imai J, Kasuga S, Matsuura H, et al. Pharmacokinetics of the garlic compound S-allylcysteine. Planta Med. 1994;60(3): 214-7.
DOI: 10.1055/s-2006-959461.

Horie T, Awazu S, Itakura Y, Fuwa T. Identified diallyl polysulfides from an aged garlic extract which protects the membranes from lipid peroxidation. Planta Med. 1992;58(5):468-9.
DOI: 10.1055/s-2006-961517.

Ide N, Lau BH. Aged garlic extract attenuates intracellular oxidative stress. Phytomedicine. 1999;6(2):125-31.
DOI: 10.1016/S0944-7113(99)80047-6

Zhang H, Wang K, Lin G, Zhao Z. Antitumor mechanisms of S-allyl mercaptocysteine for breast cancer therapy. BMC Complement Altern Med. 2014;14:270.
DOI: 10.1186/1472-6882-14-270

Hwang IG, Kim HY, Woo KS, Lee J, Jeong HS. Biological activities of Maillard reaction products (MRPs) in a sugar–amino acid model system. Food Chem. 2011;126(1): 221-27.

Park C, Park S, Chung YH, Kim GY, Choi YW, Kim BW, et al. Induction of apoptosis by a hexane extract of aged black garlic in the human leukemic U937 cells. Nutr Res Pract. 2014;8(2):132-7.
DOI: 10.4162/nrp.2014.8.2.132.

Yuan H, Sun L, Chen M, Wang J. The Comparison of the Contents of Sugar, Amadori, and Heyns Compounds in Fresh and Black Garlic. J Food Sci. 2016;81(7):C1662-8.
DOI: 10.1111/1750-3841.13365

Kim TH, Shin YJ, Won AJ, Lee BM, Choi WS, Jung JH, et al. Resveratrol enhances chemosensitivity of doxorubicin in multidrug-resistant human breast cancer cells via increased cellular influx of doxorubicin. Biochim Biophys Acta. 2014;1840(1):615-25.
DOI: 10.1016/j.bbagen.2013.10.023.

Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646-74.
DOI: 10.1016/j.cell.2011.02.013.

Purev U, Chung MJ, Oh DH. Individual differences on immunostimulatory activity of raw and black garlic extract in human primary immune cells. Immunopharmacol Immunotoxicol. 2012; 34(4):651-60.
DOI: 10.3109/08923973.2011.649288.

Tanaka S, Haruma K, Yoshihara M, Kajiyama G, Kira K, Amagase H, et al. Aged garlic extract has potential suppressive effect on colorectal adenomas in humans. J Nutr. 2006;136(3 Suppl): 821S-26S.
DOI: 10.1093/jn/136.3.821S.

Dion M, Milner J. Garlic inhibits cytochrome P450 2E1 mediated chlorzoxazone metabolism. FASEB J. 1997:2144-44.

Ng KT, Guo DY, Cheng Q, Geng W, Ling CC, Li CX, et al. A garlic derivative, S-allylcysteine (SAC), suppresses proliferation and metastasis of hepato-cellular carcinoma. PLoS One. 2012;7(2): e31655.
DOI: 10.1371/journal.pone.0031655.

Iciek M, Kwiecien I, Chwatko G, Sokolowska-Jezewicz M, Kowalczyk-Pachel D, Rokita H. The effects of garlic-derived sulfur compounds on cell proliferation, caspase 3 activity, thiol levels and anaerobic sulfur metabolism in human hepatoblastoma HepG2 cells. Cell Biochem Funct. 2012;30(3):198-204.
DOI: 10.1002/cbf.1835.

Tong D, Qu H, Meng X, Jiang Y, Liu D, Ye S, et al. S-allylmercaptocysteine promotes MAPK inhibitor-induced apoptosis by activating the TGF-beta signaling pathway in cancer cells. Oncol Rep. 2014;32(3): 1124-32.
DOI: 10.3892/or.2014.3295.

Hung TC, Lee WY, Chen KB, Chan YC, Chen CY. An investigation of small GTPases in relation to liver tumorigenesis using traditional Chinese medicine. Biomed Res Int. 2014;2014:428210.
DOI: 10.1155/2014/428210.

Wang X, Jiao F, Wang QW, Wang J, Yang K, Hu RR, et al. Aged black garlic extract induces inhibition of gastric cancer cell growth in vitro and in vivo. Mol Med Rep. 2012;5(1):66-72.
DOI: 10.3892/mmr.2011.588.

Lee Y, Kim H, Lee J, Kim K. Anticancer activity of S-allylmercapto-L-cysteine on implanted tumor of human gastric cancer cell. Biol Pharm Bull. 2011;34(5):677-81. DOI: 10.1248/bpb.34.677.

Yan JY, Tian FM, Hu WN, Zhang JH, Cai HF, Li N. Apoptosis of human gastric cancer cells line SGC 7901 induced by garlic-derived compound S-allylmercapto-cysteine (SAMC). Eur Rev Med Pharmacol Sci. 2013;17(6):745-51.

Dong M, Yang G, Liu H, Liu X, Lin S, Sun D, et al. Aged black garlic extract inhibits HT29 colon cancer cell growth via the PI3K/Akt signaling pathway. Biomed Rep. 2014;2(2):250-54.

DOI: 10.3892/br.2014.226.

Shirin H, Pinto JT, Kawabata Y, Soh JW, Delohery T, Moss SF, et al. Antiproliferative effects of S-allylmercaptocysteine on colon cancer cells when tested alone or in combination with sulindac sulfide. Cancer Res. 2001;61(2):725-31.

Xiao D, Pinto JT, Soh JW, Deguchi A, Gundersen GG, Palazzo AF, et al. 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. 2003; 63(20):6825-37.

Liang D, Qin Y, Zhao W, Zhai X, Guo Z, Wang R, et al. S-allylmercaptocysteine effectively inhibits the proliferation of colorectal cancer cells under in vitro and in vivo conditions. Cancer Lett. 2011;310(1):69-76.

DOI: 10.1016/j.canlet.2011.06.019.

Xiao D, Pinto JT, Gundersen GG, Weinstein IB. Effects of a series of organosulfur compounds on mitotic arrest and induction of apoptosis in colon cancer cells. Mol Cancer Ther. 2005;4(9):1388- 98.
DOI: 10.1158/1535-7163.MCT-05-0152.

Zhang Y, Li HY, Zhang ZH, Bian HL, Lin G. Garlic-derived compound S-allylmercaptocysteine inhibits cell growth and induces apoptosis via the JNK and p38 pathways in human colorectal carcinoma cells. Oncol Lett. 2014;8(6):2591-96.
DOI: 10.3892/ol.2014.2579.

Sigounas G, Hooker J, Anagnostou A, Steiner M. S-allylmercaptocysteine inhibits cell proliferation and reduces the viability of erythroleukemia, breast, and prostate cancer cell lines. Nutr Cancer. 1997;27(2):186-91.
DOI: 10.1080/01635589709514523.

Pinto JT, Qiao C, Xing J, Rivlin RS, Protomastro ML, Weissler ML, et al. Effects of garlic thioallyl derivatives on growth, glutathione concentration, and polyamine formation of human prostate carcinoma cells in culture. Am J Clin Nutr. 1997;66(2):398-405.
DOI: 10.1093/ajcn/66.2.398.

Pinto JT, Qiao C, Xing J, Suffoletto BP, Schubert KB, Rivlin RS, et al. Alterations of prostate biomarker expression and testosterone utilization in human LNCaP prostatic carcinoma cells by garlic-derived S-allylmercaptocysteine. Prostate. 2000;45(4):304-14.

Chu Q, Ling MT, Feng H, Cheung HW, Tsao SW, Wang X, et al. A novel anticancer effect of garlic derivatives: inhibition of cancer cell invasion through restoration of E-cadherin expression. Carcinogenesis. 2006;27(11):2180-9.
DOI: 10.1093/carcin/bgl054.

Howard EW, Ling MT, Chua CW, Cheung HW, Wang X, Wong YC. Garlic-derived S-allylmercaptocysteine is a novel in vivo antimetastatic agent for androgen-independent prostate cancer. Clin Cancer Res. 2007;13(6):1847-56.
DOI: 10.1158/1078-0432.CCR-06-2074.

Howard EW, Lee DT, Chiu YT, Chua CW, Wang X, Wong YC. Evidence of a novel docetaxel sensitizer, garlic-derived S-allylmercaptocysteine, as a treatment option for hormone refractory prostate cancer. Int J Cancer. 2008;122(9):1941-8. DOI: 10.1002/ijc.23355.

Hung TC, Lee WY, Chen KB, Chan YC, Chen CY. Investigation of estrogen receptor (ESR1) for breast cancer from traditional Chinese medicine. Biomed Res Int. 2014;2014:321486.
DOI: 10.1155/2014/321486.

Hu H, Zhang XP, Wang YL, Chua CW, Luk SU, Wong YC, et al. Identification of a novel function of Id-1 in mediating the anticancer responses of SAMC, a water-soluble garlic derivative, in human bladder cancer cells. Mol Med Rep. 2011;4(1):9-16.
DOI: 10.3892/mmr.2010.380.

Liu Y, Yan J, Han X, Hu W. Garlic-derived compound S-allylmercaptocysteine (SAMC) is active against anaplastic thyroid cancer cell line 8305C (HPACC). Technol Health Care. 2015;23 Suppl 1:S89-93.
DOI: 10.3233/thc-150936.

Wang K, Wang Y, Qi Q, Zhang F, Zhang Y, Zhu X, et al. Inhibitory effects of S-allylmercaptocysteine against benzo(a)pyrene-induced precancerous carcinogenesis in human lung cells. Int Immunopharmacol. 2016;34:37- 43.
DOI: 10.1016/j.intimp.2016.02.017.

Wu J, Zhao S, Zhang J, Qu X, Jiang S, Zhong Z, et al. Over-expression of survivin is a factor responsible for differential responses of ovarian cancer cells to S-allylmercaptocysteine (SAMC). Exp Mol Pathol. 2016;100(2):294-302.
DOI: 10.1016/j.yexmp.2016.02.003.

Xu Y, Su D, Zhu L, Zhang S, Ma S, Wu K, et al. S-allylcysteine suppresses ovarian cancer cell proliferation by DNA methylation through DNMT1. J Ovarian Res. 2018;11(1):39.
DOI: 10.1186/s13048-018-0412-1.

Xu YS, Feng JG, Zhang D, Zhang B, Luo M, Su D, et al. S-allylcysteine, a garlic derivative, suppresses proliferation and induces apoptosis in human ovarian cancer cells in vitro. Acta Pharmacol Sin. 2014;35(2):267-74.
DOI: 10.1038/aps.2013.176.

Sigounas G, Hooker JL, Li W, Anagnostou A, Steiner M. S-allylmercaptocysteine, a stable thioallyl compound, induces apoptosis in erythroleukemia cell lines. Nutr Cancer. 1997;28(2):153-9.
DOI: 10.1080/01635589709514568.

Lea MA, Rasheed M, Randolph VM, Khan F, Shareef A, desBordes C. Induction of histone acetylation and inhibition of growth of mouse erythroleukemia cells by S-allylmercaptocysteine. Nutr Cancer. 2002;43(1):90-102.
DOI: 10.1207/S15327914NC431_11.

Matsuura Y, Kawagoe T, Toki N, Tanaka M, Kashimura M. Long-standing complications after treatment for cancer of the uterine cervix--clinical significance of medical examination at 5 years after treatment. Int J Gynecol Cancer. 2006;16(1):294-7.

Xiao J, Xing F, Liu Y, Lv Y, Wang X, Ling MT, et al. Garlic-derived compound S-allylmercaptocysteine inhibits hepatocarcinogenesis through targeting LRP6/Wnt pathway. Acta Pharmaceutica Sinica B. 2018;8(4):575-86.

Nicastro HL, Ross SA, Milner JA. Garlic and onions: their cancer prevention properties. Cancer Prev Res (Phila). 2015;8(3):181-9.
DOI: 10.1158/1940-6207.CAPR-14-0172

Pedraza-Chaverri J, Barrera D, Maldonado PD, Chirino YI, Macias-Ruvalcaba NA, Medina-Campos ON, et al. S-allylmercaptocysteine scavenges hydroxyl radical and singlet oxygen in vitro and attenuates gentamicin-induced oxidative and nitrosative stress and renal damage in vivo. BMC Clin Pharmacol. 2004;4:5.
DOI: 10.1186/1472-6904-4-5

Li S, Yang G, Zhu X, Cheng L, Sun Y, Zhao Z. Combination of rapamycin and garlic-derived S-allylmercaptocysteine induces colon cancer cell apoptosis and suppresses tumor growth in xenograft nude mice through autophagy/p62/Nrf2 pathway. Oncol Rep. 2017;38(3):1637-44.
DOI: 10.3892/or.2017.5849