Advanced SearchSearch Tips
Anticarcinogenic Effect of S-allylcysteine (SAC)
facebook(new window)  Pirnt(new window) E-mail(new window) Excel Download
  • Journal title : Journal of Life Science
  • Volume 25, Issue 11,  2015, pp.1331-1337
  • Publisher : Korean Society of Life Science
  • DOI : 10.5352/JLS.2015.25.11.1331
 Title & Authors
Anticarcinogenic Effect of S-allylcysteine (SAC)
Kong, Il-Keun; Kim, Hyun Hee; Min, Gyesik;
  PDF(new window)
S-allylcysteine (SAC) is an aged garlic derived water soluble organosulfur compound and has been suggested to have anticarcinogenic activity against diverse types of cancer cells. This review summarizes the cellular signaling pathways and molecular mechanisms whereby SAC exerts its effects on cellular proliferation, apoptosis, cell cycle progression and metastasis based on the results from both in vitro and in vivo studies. SAC activates proapoptotic proteins including Bax and caspase-3, but suppresses antiapoptotic Bcl-2 family proteins to bring about cancer cell death through mitochondria-mediated intrinsic pathway. SAC also inhibits cellular proliferation by inducing cell cycle arrest in which SAC reduces expression and activation of NF-κB, cyclins, Cdks, PCNA and c-Jun, but elevates expression of cell cycle inhibitor proteins p16 and p21 through suppression of both PI3K/Akt/mTOR and MAPK/ERK signaling pathways. And, SAC inhibits invasion and metastasis of cancer cells by inducing suppression of both angiogenesis and epithelial-mesenchymal transition (EMT) through decreased cyclooxygenase (COX)-2 expression and increased E-cadherin expression which were then caused by suppression of inhibitory transcription factors Id-1 and SLUG from SAC-mediated inactivation of both MAPK/ERK and PI3K/Akt/mTOR/NF-κB signaling pathways. Furthermore, SAC prevents toxic compound-induced carcinogenesis by inducing antioxidant enzymes such as glutathione-s-transferase (GST). Thus, SAC can be considered as a potential chemotherapeutic agent for the prevention and treatment of cancer.
Apoptosis;cell cycle;cell proliferation;epithelial-mesenchymal transition (EMT);S-allylcysteine (SAC);
 Cited by
Amagase, H. and Milner, J. A. 1993. Impact of various sources of garlic and their constituents on 7,12-dimethylbenz[a] anthracene binding to mammary cell DNA. Carcinogenesis 14, 1627-1631. crossref(new window)

Balasenthil, S., Rao, K. S. and 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. crossref(new window)

Bhatia, K., Ahmad, F., Rashid, H. and Raisuddin, S. 2008. Protective effect of S-allylcysteine against cyclophosphamideinduced bladder hemorrhagic cystitis in mice. Food Chem. Toxicol. 46, 3368-3374. crossref(new window)

Birchmeier, W. and Behrens, J. 1994. Cadherin expression in carcinomas: role in the formation of cell junctions and the prevention of invasiveness. Biochim. Biophys. Acta. 1198, 11-26.

Bracke, M. E., Van, Roy. F. M. and Mareel, M. M. 1996. The E-cadherin/catenin complex in invasion and metastasis. Curr. Top Microbiol. Immunol. 213, 123-161.

Butt, M. S., Sultan, M. T., Butt, M. S. and Iqbal, J. 2009. Garlic: nature’s protection against physiological threats. Crit. Rev. Food Sci. Nutr. 49, 538-551. crossref(new window)

Cerutti, P. A. 1985. Prooxidant states and tumor promotion. Science 227, 375-381. crossref(new window)

Chu, Q., Lee, D. T., Tsao, S. W., Wang, X. and Wong, Y. C. 2007. 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, 925-932. crossref(new window)

Chu, Q., Ling, M. T., Feng, H., Cheung, H. W., Tsao, S. W., Wang, X. and Wong, Y. C. 2006. A novel anticancer effect of garlic derivatives: inhibition of cancer cell invasion through restoration of E-cadherin expression. Carcinogenesis 27, 2180-2189. crossref(new window)

Cohen, L. A., Zhao, Z., Pittman, B. and Lubet, R. 1999. S-allylcysteine, a garlic constituent, fails to inhibit N-methylnitrosourea-induced rat mammary tumorigenesis. Nutr. Cancer 35, 58-63. crossref(new window)

Conacci-Sorrell, M., Simcha, I., Ben-Yedidia, T., Blechman, J., Savagner, P. and Ben-Ze’ev, A. 2003. Autoregulation of E-cadherin expression by cadherin-cadherin interactions: the roles of beta-catenin signaling, Slug, and MAPK. J. Cell Biol. 163, 847-857. crossref(new window)

Dohadwala, M., Wang, G., Heinrich, E., Luo, J., Lau, O., Shih, H., Munaim, Q., Lee, G., Hong, L., Lai, C., Abemayor, E., Fishbein, M. C., Elashoff, D. A., Dubinett, S. M. and St. John, M. A. 2010. The role of ZEB1 in the inflammation-induced promotion of EMT in HNSCC. Otolaryngol. Head Neck Surg. 142, 753-759. crossref(new window)

Fleischauer, A. T. and Arab, L. 2001. Garlic and cancer: a critical review of the epidemiologic literature. J. Nutr. 131, 1032S-1040S.

Fresno Vara, J. A., Casado, E., de, Castro. J., Cejas, P., BeldaIniesta, C. and González-Barón, M. 2004. PI3K/Akt signalling pathway and cancer. Cancer Treat Rev. 30, 193-204. crossref(new window)

Gapter, L. A., Yuin, O. Z. and Ng, K. Y. 2008. S-Allylcysteine reduces breast tumor cell adhesion and invasion. Biochem. Biophys. Res. Commun. 367, 446-451. crossref(new window)

Hanahan, D. and Weinberg, R. A. 2000. The hallmarks of cancer. Cell 100, 57-70. crossref(new window)

Hatono, S. and Wargovich, M. J. 1997. Role of garlic in disease prevention-preclinical models. Nutraceuticals: Designer Foods III: Garlic, Soy and Licorice. 139-151.

Herman-Antosiewicz, A. and Singh, S. V. 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. crossref(new window)

Hsing, A. W., Chokkalingam, A. P., Gao, Y. T., Madigan, M. P., Deng, J., Gridley, G. and Fraumeni, J. F. Jr. 2002. Allium vegetables and risk of prostate cancer: a population-based study. J. Natl. Cancer Inst. 94, 1648-1651. crossref(new window)

Iciek, M., Kwiecien, I., Chwatko, G., Sokolowska-Jezewicz, M., Kowalczyk-Pachel, D. and Rokita, H. 2011. 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. 30, 198-204.

Jang, T. J., Jeon, K. H. and Jung, K. H. 2009. Cyclooxygenase-2 expression is related to the epithelial-to-mesenchymal transition in human colon cancers. Yonsei Med. J. 50, 818-824. crossref(new window)

Jayasurya, R., Francis, G., Kannan, S., Lekshminarayanan, K., Nalinakumari, K. R., Abraham, T., Abraham, E. K. and Nair, M. K. 2004. p53, p16 and cyclin D1: molecular determinants of radiotherapy treatment response in oral carcinoma. Int. J. Cancer 109, 710-716. crossref(new window)

Jethwa, P., Naqvi, M., Hardy, R. G., Hotchin, N. A., Roberts, S., Spychal, R. and Tselepis, C. 2008. Overexpression of Slug is associated with malignant progression of esophageal adenocarcinoma. World J. Gastroenterol. 14, 1044-1052. crossref(new window)

Jordà, M., Vinyals, A., Marazuela, A., Cubillo, E., Olmeda, D., Valero, E., Cano, A. and Fabra, A. 2007. Id-1 is induced in MDCK epithelial cells by activated Erk/MAPK pathway in response to expression of the Snail and E47 transcription factors. Exp. Cell Res. 313, 2389-2403. crossref(new window)

Kim, H. H. and Min, G. S. 2015. Inhibitory effects of S-allylcysteine on cell proliferation of human cervical cancer cell line, HeLa. J. Life Sci. 25, 397-405. crossref(new window)

Kodera, Y., Suzuki, A., Imada, O., Kasugai, S., Smoke, I., Kanezawa, A., Taru, N., Fujikawa, M., Nagae, S., Masamoto, K., Maeshige, K. and Ono, K. 2002. Physical, chemical, and biological properties of s-allylcysteine, an amino acid derived from garlic. J. Agric. Food Chem. 50, 622-632. crossref(new window)

Lapenna, S. and Giordano, A. 2009. Cell cycle kinases as therapeutic targets for cancer. Nat. Rev. Drug Discov. 8, 547-566. crossref(new window)

Lee, B. H. and Lee, S. J. 1999. Preventive effects of a mixed disulphide from dithiocarbamate and N-acetylcysteine on the genotoxicity of N-nitrosodiethylamine. J. Pharm. Pharmacol. 51, 105-109.

Li, Y. J., Wei, Z. M., Meng, Y. X. and Ji, X. R. 2005. Beta-catenin up-regulates the expression of cyclinD1, c-myc and MMP-7 in human pancreatic cancer: relationships with carcinogenesis and metastasis. World J. Gastroenterol. 11, 2117-2123. crossref(new window)

Liu, Z., Li, M., Chen, K., Yang, J., Chen, R., Wang, T., Liu, J., Yang, W. and Ye, Z. 2012. S-allylcysteine induces cell cycle arrest and apoptosis in androgen-indipendent human prostate cancer cells. Mol. Med. Rep. 5, 439-443.

Llambi, F. and Green, D. R. 2011. Apoptosis and oncogenesis: give and take in the BCL-2 family. Curr. Opin. Genet. Dev. 21, 12-20. crossref(new window)

Loeppky, R. N. and Li, Y. E. 1991. Nitrosamine activation and detoxication through free radicals and their derived cations. IARC Sci. Publ. 105, 375-382.

Malumbres, M. and Barbacid, M. 2009. Cell cycle, CDKs and cancer: a changing paradigm. Nat. Rev. Cancer 9, 153-166. crossref(new window)

Martin, K. R. 2006. Targeting apoptosis with dietary bioactive agents. Exp. Biol. Med. (Maywood). 231, 117-129.

McCubrey, J. A., Steelman, L. S., Chappell, W. H., Abrams, S. L., Wong, E. W., Chang, F., Lehmann, B., Terrian, D. M., Milella, M., Tafuri, A., Stivala, F., Libra, M., Basecke, J., Evangelisti, C., Martelli, A. M. and Franklin, R. A. 2007. Roles of the Raf/MEK/ERK pathway in cell growth, malignant transformation and drug resistance. Biochim. Biophys. Acta. 1773, 1263-1284. crossref(new window)

Moriguchi, T., Matsuura, H., Kodera, Y., Itakura, Y., Katsuki, H., Saito, H. and Nishiyama, N. 1997. Neurotrophic activity of organosulfur compounds having a thioallyl group on cultured rat hippocampal neurons. Neurochem. Res. 22, 1449-1452. crossref(new window)

Na, H. K., Kim, E. H., Choi, M. A., Park, J. M., Kim, D. H. and Surh, Y. J. 2012. Diallyl trisulfide induces apoptosis in human breast cancer cells through ROS-mediated activation of JNK and AP-1. Biochem. Pharmacol. 84, 1241-1250. crossref(new window)

Nagae, S., Ushijima, M., Hatono, S., Imai, J., Kasugai, S., Matsuura, H., Itakura, Y. and Higashi, Y. 1994. Pharmacokinetics of the garlic compound S-allylcysteine. Planta. Med. 60, 214-217. crossref(new window)

Neal, C. L., Mckeithen, D. and Odero-Marah, V. A. 2011. Snail negatively regulates cell adhesion to extracellular matrix and integrin expression via the MAPK pathway in prostate cancer cells. Cell Adh. Migr. 5, 249-257. crossref(new window)

Ng, K. T., Guo, D. Y., Cheng, Q., Geng, W., Ling, C. C., Li, C. X., Liu, X. B., Ma, Y. Y., Lo, C. M., Poon, R. T., Fan, S. T and Man, K. 2012. A garlic derivative, S-allylcysteine (SAC), suppresses proliferation and metastasis of hepatocellular carcinoma. PLoS One 7, e31655. crossref(new window)

Nicholson, K. M. and Anderson, N. G. 2002. The protein kinase B/Akt signalling pathway in human malignancy. Cell Signal 14, 381-395. crossref(new window)

Noori, S. and Hassan, Z. M. 2012. Tehranolide inhibits proliferation of MCF-7 human breast cancer cells by inducing G0/G1 arrest and apoptosis. Free Radic. Biol. Med. 52, 1987-1999. crossref(new window)

Oberley, L. W. and Buettner, G. R. 1979. Role of superoxide dismutase in cancer: a review. Cancer Res. 39, 1141-1149.

Oyama, T., Kanai, Y., Ochiai, A., Akimoto, S., Oda, T., Yanagihara, K., Nagafuchi, A., Tsukita, S., Shibamoto, S., Ito, F. and Takeichi, M., Matsuda, H. and Hirohashi, S. 1994. A truncated beta-catenin disrupts the interaction between E-cadherin and alpha-catenin: a cause of loss of intercellular adhesiveness in human cancer cell lines. Cancer Res. 54, 6282-6287.

Pagliei, B., Aquilano, K., Baldelli, S. and Ciriolo, M. R. 2013. Garlic-derived diallyl disulfide modulates peroxisome proliferator activated receptor gamma co-activator 1 alpha in neuroblastoma cells. Biochem. Pharmacol. 85, 335-344. crossref(new window)

Pai, M. H., Kuo, Y. H., Chiang, E. P. and Tang, F. Y. 2012. S-Allylcysteine inhibits tumour progression and the epithelial-mesenchymal transition in a mouse xenograft model of oral cancer. Br. J. Nutr. 108, 28-38. crossref(new window)

Philchenkov, A. 2004. Caspases: potential targets for regulating cell death. J. Cell. Mol. Med. 8, 432-444. crossref(new window)

Powolny, A. A. and Singh, S. V. 2008. Multitargeted prevention and therapy of cancer by diallyl trisulfide and related Allium vegetable-derived organosulfur compounds. Cancer Lett. 269, 305-314. crossref(new window)

Reed, J. C. 2006. Proapoptotic multidomain Bcl-2/Bax-family proteins: mechanisms, physiological roles, and therapeutic opportunities. Cell Death Differ. 13, 1378-1386. crossref(new window)

Sartor, M., Steingrimsdottir, H., Elamin, F., Gäken, J., Warnakulasuriya, S., Partridge, M., Thakker, N., Johnson, N. W. and Tavassoli, M. 1999. Role of p16/MTS1, cyclin D1 and RB in primary oral cancer and oral cancer cell lines. Br. J. Cancer 80, 79-86. crossref(new window)

Sundaresan, S. and Subramanian, P. 2008. Prevention of N-nitrosodiethylamine-induced hepatocarcinogenesis by S-allylcysteine. Mol. Cell Biochem. 310, 209-214. crossref(new window)

Takayama, T., Shiozaki, H., Shibamoto, S., Oka, H., Kimura, Y., Tamura, S., Inoue, M., Monden, T., Ito, F. and Monden, M. 1996. Beta-catenin expression in human cancers. Am. J. Pathol. 148, 39-46.

Tanaka, S., Haruma, K., Yoshihara, M., Kajiyama, G., Kira, K., Amagase, H. and Chayama, K. 2006. Aged garlic extract has potential suppressive effect on colorectal adenomas in humans. J. Nutr. 136, 821S-826S.

Tang, F. Y., Chiang, E. P. and Pai, M. H. 2010. Consumption of S-allylcysteine inhibits the growth of human non-smallcell lung carcinoma in a mouse xenograft model. J. Agric. Food Chem. 58, 11156-11164. crossref(new window)

Tang, F. Y., Chiang, E. P., Chung, J. G., Lee, H. Z. and Hsu, C. Y. 2009. S-allylcysteine modulates the expression of E-cadherin and inhibits the malignant progression of human oral cancer. J. Nutr. Biochem. 20, 1013-1020. crossref(new window)

Taylor, R. C., Cullen, S. P. and Martin, S. J. 2008. Apoptosis: controlled demolition at the cellular level. Nat. Rev. Mol. Cell Biol. 9, 231-241. crossref(new window)

Thomas, G. J. and Speight, P. M. 2001. Cell adhesion molecules and oral cancer. Crit. Rev. Oral Biol. Med. 12, 479-498. crossref(new window)

Thomson, M. and Ali, M. 2003. Garlic [Allium sativum]: a review of its potential use as an anti-cancer agent. Curr. Cancer Drug Targets 3, 67-81. crossref(new window)

Todd, R., Hinds, P. W., Munger, K., Rustgi, A. K., Opitz, O. G., Suliman, Y. and Wong, D. T. 2002. Cell cycle dysregulation in oral cancer. Crit. Rev. Oral Biol. Med. 13, 51-61. crossref(new window)

Van Aken, E., De Wever, O., Correia da Rocha, A. S. and Mareel, M. 2001. Defective E-cadherin/catenin complexes in human cancer. Virchows Arch. 439, 725-751. crossref(new window)

Velmurugan, B., Mani, A. and 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, 387-393. crossref(new window)

Vivanco, I. and Sawyers, C. L. 2002. The phosphatidylinositol 3-Kinase AKT pathway in human cancer. Nat. Rev. Cancer 2, 489-501. crossref(new window)

Welch, C., Wuarin, L. and Sidell, N. 1992. Antiproliferative effect of the garlic compound S-allyl cysteine on human neuroblastoma cells in vitro. Cancer Lett. 63, 211-219. crossref(new window)

Xu, Y. S., Feng, J. G., Zhang, D., Luo, M., Su, D. and Lin, N. M. 2014. S-allylcysteine, a garlic derivative, suppresses proliferation and induces apoptosis in human ovarian cancer cells in vitro. Acta. Pharmacol. Sin. 35, 267-274. crossref(new window)

Zhou, Y., Zhuang, W., Hu, W., Liu, G. J., Wu, T. X. and Wu, X. T. 2011. Consumption of large amounts of Allium vegetables reduces risk for gastric cancer in a meta-analysis. Gastroenterology 141, 80-89. crossref(new window)