Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry


ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Review Article

Garlic and its Active Compounds: A Potential Candidate in The Prevention of Cancer by Modulating Various Cell Signalling Pathways

Author(s): Saleh A. Almatroodi, Mohammed A. Alsahli, Ahmad Almatroudi and Arshad H. Rahmani*

Volume 19 , Issue 11 , 2019

Page: [1314 - 1324] Pages: 11

DOI: 10.2174/1871520619666190409100955

Price: $65


Background: Cancer is a multi-factorial disease including alterations in the cell signalling pathways. Currently, several drugs are in use to treat cancer but such drugs show negative side effects on normal cells and cause severe toxicity.

Methods: The current research is mainly focused on medicinal plants with potential therapeutic efficacy in the treatment of cancer without any adverse effects on normal cells. In this regard, garlic and its active compounds including diallyl sulfide, diallyl trisulfide, ajoene, and allicin have been established to suppress the growth of cancer and killing of cancer cells.

Result: The review focuses on garlic and its active compounds chemopreventive effect through modulating various cell signalling pathways. Additionally, garlic and its active compound were established to induce cell cycle arrest at the G0/G1 phase and G2/M phases in cancer cells, increase the expression of tumor suppressor genes, inhibit the angiogenesis process, induction of apoptosis and modulation of various other genetic pathways.

Conclusion: This review sketches the diverse chemopreventive activities of garlic and their active ingredients in the management of cancer mainly focusing on cell signalling pathways.

Keywords: Garlic, allicin, diallyl disulfide, diallyl trisulfide, apoptosis, angiogenesis, cell signalling pathways.

Graphical Abstract
Katiyar, S.K. UV-induced immune suppression and photocarcinogenesis: Chemoprevention by dietary botanical agents. Cancer Lett., 2007, 255(1), 1-11.
Nichols, J.A.; Katiyar, S.K. Skin photoprotection by natural polyphenols: Anti-inflammatory, antioxidant and DNA repair mechanisms. Arch. Dermatol. Res., 2010, 302(2), 71-83.
Londhe, V.; Gavasane, A.T. Role of garlic (Allium sativum) in various diseases: An overview. J. Pharmaceut. Res. Opinion, 2011, 1, 129-134.
Raghu, R.; Lu, K.H.; Sheen, L.Y. Recent research progress on garlic (da suan) as a potential anticarcinogenic agent against major digestive cancers. J. Tradit. Complement. Med., 2012, 2(3), 192-201.
Chung, L.Y. The antioxidant properties of garlic compounds: Allyl cysteine, alliin, allicin, and allyl disulfide. J. Med. Food, 2006, 9(2), 205-213.
Kim, S.R.; Jung, Y.R.; An, H.J.; Kim, D.H.; Jang, E.J.; Choi, Y.J.; Moon, K.M.; Park, M.H.; Park, C.H.; Chung, K.W.; Bae, H.R.; Choi, Y.W.; Kim, N.D.; Chung, H.Y. Anti-wrinkle and anti-inflammatory effects of active garlic components and the inhibition of MMPs via NF-kappaB signaling. PLoS One, 2013, 8(9)e73877
Vazquez-Prieto, M.A.; Rodriguez Lanzi, C.; Lembo, C.; Galmarini, C.R.; Miatello, R.M. Garlic and onion attenuates vascular inflammation and oxidative stress in fructose-fed rats. J. Nutr. Metab., 2011, 2011475216
Shin, S.S.; Song, J.H.; Hwang, B.; Noh, D.H.; Park, S.L.; Kim, W.T.; Park, S.S.; Kim, W.J.; Moon, S.K. HSPA6 augments garlic extract-induced inhibition of proliferation, migration, and invasion of bladder cancer EJ cells; Implication for cell cycle dysregulation, signaling pathway alteration, and transcription factor-associated MMP-9 regulation. PLoS One, 2017, 12(2)e0171860
Singh, S.V.; Mohan, R.R.; Agarwal, R.; Benson, P.J.; Hu, X.; Rudy, M.A.; Xia, H.; Katoh, A.; Srivastava, S.K.; Mukhtar, H.; Gupta, V.; Zaren, H.A. 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., 1996, 225(2), 660-665.
Singh, S.V. Impact of garlic organosulfides on p21(H-ras) processing. J. Nutr., 2001, 131(3s), 1046s-1048s.
Newall, C.A.; Anderson, L.A.; Phillipson, J.D. Herbal Medicines. A Guide for Health-Care Professionals; The Pharmaceutical Press, 1996.
Omar, S.; Al-Wabel, N. Organosulfur compounds and possible mechanism of garlic in cancer. Saudi Pharm. J., 2010, 18(1), 51-58.
Block, E.; Naganathan, S.; Putman, D.; Zhao, S-H. Organosulfur chemistry of garlic and onion: Recent results. Pure Appl. Chem., 1993, 65(4), 625-632.
Mostafa, R.M.; Moustafa, Y.M.; Mirghani, Z.; AlKusayer, G.M.; Moustafa, K.M. Antioxidant effect of garlic (Allium sativum) and black seeds (Nigella sativa) in healthy postmenopausal women. SAGE Open Med., 2013, 12050312113517501
Kim, S.M.; Kubota, K.; Kobayashi, A. Antioxidative activity of sulfur-containing flavor compounds in garlic. Biosci. Biotechnol. Biochem., 1997, 61(9), 1482-1485.
Rabinkov, A.; Miron, T.; Konstantinovski, L.; Wilchek, M.; Mirelman, D.; Weiner, L. The mode of action of allicin: Trapping of radicals and interaction with thiol containing proteins. Biochim. Biophys. Acta (BBA)-. General Subj., 1998, 1379(2), 233-244.
Dhawan, V.; Jain, S. Garlic supplementation prevents oxidative DNA damage in essential hypertension. Mol. Cell. Biochem., 2005, 275(1-2), 85-94.
Nencini, C.; Menchiari, A.; Franchi, G.G.; Micheli, L. In vitro antioxidant activity of aged extracts of some Italian Allium species. Plant Foods Hum. Nutr., 2011, 66(1), 11-16.
Lawal, A.O.; Lawal, A.F.; Ologundudu, A.; Adeniran, O.Y.; Omonkhua, A.; Obi, F. Antioxidant effects of heated garlic juice on cadmium-induced liver damage in rats as compared to ascorbic acid. J. Toxicol. Sci., 2011, 36(5), 549-557.
Kay, H.Y.; Won Yang, J.; Kim, T.H.; Lee, D.Y.; Kang, B.; Ryu, J-H.; Jeon, R.; Kim, S.G. Ajoene, a stable garlic by-product, has an antioxidant effect through Nrf2-mediated glutamate-cysteine ligase induction in HepG2 cells and primary hepatocytes. J. Nut., 2010, 140(7), 1211-1219.
Shankar, S.; Chen, Q.; Ganapathy, S.; Singh, K.P.; Srivastava, R.K. Diallyl trisulfide increases the effectiveness of TRAIL and inhibits prostate cancer growth in an orthotopic model: Molecular mechanisms. Mol. Cancer Ther., 2008, 7(8), 2328-2338.
Xiao, D.; Herman-Antosiewicz, A.; Antosiewicz, J.; Xiao, H.; Brisson, M.; Lazo, J.S.; Singh, S.V. 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, 2005, 24(41), 6256-6268.
Xiao, D.; Choi, S.; Johnson, D.E.; Vogel, V.G.; Johnson, C.S.; Trump, D.L.; Lee, Y.J.; Singh, S.V. 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, 2004, 23(33), 5594-5606.
Borkowska, A.; Knap, N.; Antosiewicz, J. Diallyl trisulfide is more cytotoxic to prostate cancer cells PC-3 than to noncancerous epithelial cell line PNT1A: A possible role of p66Shc signaling axis. Nutr. Cancer, 2013, 65(5), 711-717.
Shin, D.Y.; Kim, G.Y.; Hwang, H.J.; Kim, W.J.; Choi, Y.H. Diallyl trisulfide-induced apoptosis of bladder cancer cells is caspase-dependent and regulated by PI3K/Akt and JNK pathways. Environ. Toxicol. Pharmacol., 2014, 37(1), 74-83.
Wang, Y.B.; Qin, J.; Zheng, X.Y.; Bai, Y.; Yang, K.; Xie, L.P. Diallyl trisulfide induces Bcl-2 and caspase-3-dependent apoptosis via downregulation of Akt phosphorylation in human T24 bladder cancer cells. Phytomedicine, 2010, 17(5), 363-368.
Hosono, T.; Fukao, T.; Ogihara, J.; Ito, Y.; Shiba, H.; Seki, T.; Ariga, T. Diallyl trisulfide suppresses the proliferation and induces apoptosis of human colon cancer cells through oxidative modification of beta-tubulin. J. Biol. Chem., 2005, 280(50), 41487-41493.
Yu, C.S.; Huang, A.C.; Lai, K.C.; Huang, Y.P.; Lin, M.W.; Yang, J.S.; Chung, J.G. Diallyl trisulfide induces apoptosis in human primary colorectal cancer cells. Oncol. Rep., 2012, 28(3), 949-954.
Knowles, L.M.; Milner, J.A. Diallyl disulfide induces ERK phosphorylation and alters gene expression profiles in human colon tumor cells. J. Nutr., 2003, 133(9), 2901-2906.
Farhadi, F.; Jahanpour, S.; Hazem, K.; Aghbali, A.; Baradran, B.; Pakdel, S.M.V. Garlic (Allium sativum) fresh juice induces apoptosis in human oral squamous cell carcinoma: The involvement of Caspase-3, Bax and Bcl-2. J. Dent. Res. Dent. Clin. Dent. Prospect., 2015, 9(4), 267.
Xu, Y.S.; Feng, J.G.; Zhang, D.; Zhang, B.; Luo, M.; Su, D.; Lin, N.M. S-allylcysteine, a garlic derivative, suppresses proliferation and induces apoptosis in human ovarian cancer cells in vitro. Acta Pharmacol. Sin., 2014, 35(2), 267-274.
Xu, Y.; Su, D.; Zhu, L.; Zhang, S.; Ma, S.; Wu, K.; Yuan, Q.; Lin, N. S-allylcysteine suppresses ovarian cancer cell proliferation by DNA methylation through DNMT1. J. Ovarian Res., 2018, 11(1), 39.
Su, B.; Su, J.; He, H.; Wu, Y.; Xia, H.; Zeng, X.; Dai, W.; Ai, X.; Ling, H.; Jiang, H.; Su, Q. Identification of potential targets for diallyl disulfide in human gastric cancer MGC-803 cells using proteomics approaches. Oncol. Rep., 2015, 33(5), 2484-2494.
Su, B.; Su, J.; Zeng, Y.; Liu, F.; Xia, H.; Ma, Y.H.; Zhou, Z.G.; Zhang, S.; Yang, B.M.; Wu, Y.H.; Zeng, X.; Ai, X.H.; Ling, H.; Jiang, H.; Su, Q. Diallyl disulfide suppresses epithelial-mesenchymal transition, invasion and proliferation by downregulation of LIMK1 in gastric cancer. Oncotarget, 2016, 7(9), 10498-10512.
Ling, H.; Zhang, L.Y.; Su, Q.; Song, Y.; Luo, Z.Y.; Zhou, X.T.; Zeng, X.; He, J.; Tan, H.; Yuan, J.P. Erk is involved in the differentiation induced by diallyl disulfide in the human gastric cancer cell line MGC803. Cell. Mol. Biol. Lett., 2006, 11(3), 408-423.
Li, Y.; Wang, Z.; Li, J.; Sang, X. Diallyl disulfide suppresses FOXM1-mediated proliferation and invasion in osteosarcoma by upregulating miR-134. J. Cell. Biochem., 2018.
Xie, W.P.; Zhang, Y.; Zhang, Y.K.; Li, G.; Xin, J.; Bi, R.X.; Li, C.J. Treatment of Saos-2 osteosarcoma cells with diallyl trisulfide is associated with an increase in calreticulin expression. Exp. Ther. Med., 2018, 15(6), 4737-4742.
Yu, F.S.; Wu, C.C.; Chen, C.T.; Huang, S.P.; Yang, J.S.; Hsu, Y.M.; Wu, P.P.; Ip, S.W.; Lin, J.P.; Lin, J.G.; Chung, J.G. Diallyl sulfide inhibits murine WEHI-3 leukemia cells in BALB/c mice in vitro and in vivo. Hum. Exp. Toxicol., 2009, 28(12), 785-790.
Yang, J.S.; Kok, L.F.; Lin, Y.H.; Kuo, T.C.; Yang, J.L.; Lin, C.C.; Chen, G.W.; Huang, W.W.; Ho, H.C.; Chung, J.G. Diallyl disulfide inhibits WEHI-3 leukemia cells in vivo. Anticancer Res., 2006, 26(1a), 219-225.
Suangtamai, T.; Tanyong, D.I. Diallyl disulfide induces apoptosis and autophagy via mTOR pathway in myeloid leukemic cell line. Tumour Biol., 2016, 37(8), 10993-10999.
Ma, H-B.; Huang, S.; Yin, X-R.; Zhang, Y.; Di, Z-L. Apoptotic pathway induced by diallyl trisulfide in pancreatic cancer cells. World J. Gastroenterol.: WJG, 2014, 20(1), 193.
Wang, H.C.; Yang, J.H.; Hsieh, S.C.; Sheen, L.Y. Allyl sulfides inhibit cell growth of skin cancer cells through induction of DNA damage mediated G2/M arrest and apoptosis. J. Agric. Food Chem., 2010, 58(11), 7096-7103.
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. A garlic derivative, S-allylcysteine (SAC), suppresses proliferation and metastasis of hepatocellular carcinoma. PLoS One, 2012, 7(2)e31655
Chu, Y-L.; Ho, C-T.; Chung, J-G.; Rajasekaran, R.; Sheen, L-Y. Allicin induces p53-mediated autophagy in Hep G2 human liver cancer cells. J. Agric. Food Chem., 2012, 60(34), 8363-8371.
Xiao, D.; Zeng, Y.; Hahm, E.R.; Kim, Y.A.; Ramalingam, S.; Singh, S.V. Diallyl trisulfide selectively causes Bax- and Bak-mediated apoptosis in human lung cancer cells. Environ. Mol. Mutagen., 2009, 50(3), 201-212.
Wu, P.P.; Chung, H.W.; Liu, K.C.; Wu, R.S.; Yang, J.S.; Tang, N.Y.; Lo, C.; Hsia, T.C.; Yu, C.C.; Chueh, F.S.; Lin, S.S.; Chung, J.G. Diallyl sulfide induces cell cycle arrest and apoptosis in HeLa human cervical cancer cells through the p53, caspase- and mitochondria-dependent pathways. Int. J. Oncol., 2011, 38(6), 1605-1613.
Chiu, T.H.; Lan, K.Y.; Yang, M.D.; Lin, J.J.; Hsia, T.C.; Wu, C.T.; Yang, J.S.; Chueh, F.S.; Chung, J.G. Diallyl sulfide promotes cell-cycle arrest through the p53 expression and triggers induction of apoptosis via caspase- and mitochondria-dependent signaling pathways in human cervical cancer Ca Ski cells. Nutr. Cancer, 2013, 65(3), 505-514.
Tao, Q.; Wu, C.; Xu, R.; Niu, L.; Qin, J.; Liu, N.; Zhang, P.; Wang, C. Diallyl trisulfide inhibits proliferation, invasion and angiogenesis of glioma cells by inactivating Wnt/beta-catenin signaling. Cell Tissue Res., 2017, 370(3), 379-390.
Filomeni, G.; Aquilano, K.; Rotilio, G.; Ciriolo, M.R. Reactive oxygen species-dependent c-Jun NH2-terminal kinase/c-Jun signaling cascade mediates neuroblastoma cell death induced by diallyl disulfide. Cancer Res., 2003, 63(18), 5940-5949.
Xiao, X.; Chen, B.; Liu, X.; Liu, P.; Zheng, G.; Ye, F.; Tang, H.; Xie, X. Diallyl disulfide suppresses SRC/Ras/ERK signaling-mediated proliferation and metastasis in human breast cancer by up-regulating miR-34a. PLoS One, 2014, 9(11)e112720
Altonsy, M.O.; Habib, T.N.; Andrews, S.C. Diallyl disulfide-induced apoptosis in a breast-cancer cell line (MCF-7) may be caused by inhibition of histone deacetylation. Nutr. Cancer, 2012, 64(8), 1251-1260.
Lei, X.Y.; Yao, S.Q.; Zu, X.Y.; Huang, Z.X.; Liu, L.J.; Zhong, M.; Zhu, B.Y.; Tang, S.S.; Liao, D.F. Apoptosis induced by diallyl disulfide in human breast cancer cell line MCF-7. Acta Pharmacol. Sin., 2008, 29(10), 1233-1239.
Arora, A.; Siddiqui, I.A.; Shukla, Y. Modulation of p53 in 7,12-dimethylbenz[a]anthracene-induced skin tumors by diallyl sulfide in Swiss albino mice. Mol. Cancer Ther., 2004, 3(11), 1459-1466.
Chunfeng, Y.; Aihua, H.; Yuejun, M.; Wei, L.; Laifu, L. Inhibitory effects of black garlic extracting solution on the growth of mice colon cancer Ht-29. Med. Plant, 2015, 6, 4-7.
Dong, M.; Yang, G.; Liu, H.; Liu, X.; Lin, S.; Sun, D.; Wang, Y. Aged black garlic extract inhibits HT29 colon cancer cell growth via the PI3K/Akt signaling pathway. Biomed. Rep., 2014, 2(2), 250-254.
Sagar, S.M.; Yance, D.; Wong, R. Natural health products that inhibit angiogenesis: A potential source for investigational new agents to treat cancer-part 1. Curr. Oncol., 2006, 13(1), 14.
Rahmani, A.H.; Al Zohairy, M.A.; Aly, S.M.; Khan, M.A. Curcumin: A potential candidate in prevention of cancer via modulation of molecular pathways. BioMed Res. Int., 2014, 2014761608
Rahmani, A.H.; Allemailem, K.S.; Aly, S.M.; Khan, M.A. Implications of green tea and its constituents in the prevention of cancer via the modulation of cell signalling pathway. BioMed Res. Int., 2015, 2015925640
Mousa, A.S.; Mousa, S.A. Anti-angiogenesis efficacy of the garlic ingredient alliin and antioxidants: Role of nitric oxide and p53. Nutr. Cancer, 2005, 53(1), 104-110.
Matsuura, N.; Miyamae, Y.; Yamane, K.; Nagao, Y.; Hamada, Y.; Kawaguchi, N.; Katsuki, T.; Hirata, K.; Sumi, S-I.; Ishikawa, H. Aged garlic extract inhibits angiogenesis and proliferation of colorectal carcinoma cells. J. Nutr., 2006, 136(3), 842S-846S.
Talib, W.H. Consumption of garlic and lemon aqueous extracts combination reduces tumor burden by angiogenesis inhibition, apoptosis induction, and immune system modulation. Nutrition, 2017, 43, 89-97.
Shiju, T.; Rajkumar, R.; Rajesh, N.; Viswanathan, P. Aqueous extract of Allium sativum L bulbs offer nephroprotection by attenuating vascular endothelial growth factor and extracellular signal-regulated kinase-1 expression in diabetic rats. Indian J. Exp. Biol., 2013, 51(2), 139-148.
Xiao, D.; Li, M.; Herman-Antosiewicz, A.; Antosiewicz, J.; Xiao, H.; Lew, K.L.; Zeng, Y.; Marynowski, S.W.; Singh, S.V. 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, 2006, 55(1), 94-107.
Song, B.; Shu, Y.; Cui, T.; Fu, P. Allicin inhibits human renal clear cell carcinoma progression via suppressing HIF pathway. Int. J. Clin. Exp. Med., 2015, 8(11), 20573.
Li, Y.; Zhang, J.; Zhang, L.; Si, M.; Yin, H.; Li, J. Diallyl trisulfide inhibits proliferation, invasion and angiogenesis of osteosarcoma cells by switching on suppressor microRNAs and inactivating of Notch-1 signaling. Carcinogenesis, 2013, 34(7), 1601-1610.
Lai, K.C.; Hsu, S.C.; Yang, J.S.; Yu, C.C.; Lein, J.C.; Chung, J.G. 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., 2015, 19(2), 474-484.
Oommen, S.; Anto, R.J.; Srinivas, G.; Karunagaran, D. Allicin (from garlic) induces caspase-mediated apoptosis in cancer cells. Eur. J. Pharmacol., 2004, 485(1-3), 97-103.
Xiao, D.; Pinto, J.T.; Soh, J-W.; Deguchi, A.; Gundersen, G.G.; Palazzo, A.F.; Yoon, J-T.; Shirin, H.; Weinstein, I.B. Induction of apoptosis by the garlic-derived compound S-allylmercaptocysteine (SAMC) is associated with microtubule depolymerization and c-Jun NH2-terminal kinase 1 activation. Cancer Res., 2003, 63(20), 6825-6837.
Yan, J.; Tian, F.; Hu, W.; Zhang, J.; Cai, H.; Li, N. Apoptosis of human gastric cancer cells line SGC 7901 induced by garlic-derived compound S-allylmercaptocysteine (SAMC). Eur. Rev. Med. Pharmacol. Sci., 2013, 17(6), 745-751.
Su, C-C.; Chen, G-W.; Tan, T-W.; Lin, J-G.; Chung, J-G. Crude extract of garlic induced caspase-3 gene expression leading to apoptosis in human colon cancer cells. In Vivo, 2006, 20(1), 85-90.
Zhang, Y.; Li, H.Y.; Zhang, Z.H.; Bian, H.L.; 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), 2591-2596.
Tong, D.; Qu, H.; Meng, X.; Jiang, Y.; Liu, D.; Ye, S.; Chen, H.; Jin, Y.; Fu, S.; Geng, J. S-allylmercaptocysteine promotes MAPK inhibitor-induced apoptosis by activating the TGF-beta signaling pathway in cancer cells. Oncol. Rep., 2014, 32(3), 1124-1132.
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), 1637-1644.
Jeong, J.W.; Park, S.; Park, C.; Chang, Y.C.; Moon, D.O.; Kim, S.O.; Kim, G.Y.; Cha, H.J.; Kim, H.S.; Choi, Y.W.; Kim, W.J.; Yoo, Y.H.; Choi, Y.H. N-benzyl-N-methyldecan-1-amine, a phenylamine derivative isolated from garlic cloves, induces G2/M phase arrest and apoptosis in U937 human leukemia cells. Oncol. Rep., 2014, 32(1), 373-381.
Keiss, H.P.; Dirsch, V.M.; Hartung, T.; Haffner, T.; Trueman, L.; Auger, J.; Kahane, R.; Vollmar, A.M. Garlic (Allium sativum L.) modulates cytokine expression in lipopolysaccharide-activated human blood thereby inhibiting NF-kappaB activity. J. Nutr., 2003, 133(7), 2171-2175.
Saud, S.M.; Li, W.; Gray, Z.; Matter, M.S.; Colburn, N.H.; Young, M.R.; Kim, Y.S. Diallyl Disulfide (DADS), a constituent of garlic, inactivates NF-kappaB and prevents colitis-induced colorectal cancer by inhibiting GSK-3beta. Cancer Prev. Res. (Phila.), 2016, 9(7), 607-615.
Ban, J.O.; Yuk, D.Y.; Woo, K.S.; Kim, T.M.; Lee, U.S.; Jeong, H.S.; Kim, D.J.; Chung, Y.B.; Hwang, B.Y.; Oh, K.W.; Hong, J.T. Inhibition of cell growth and induction of apoptosis via inactivation of NF-kappaB by a sulfurcompound isolated from garlic in human colon cancer cells. J. Pharmacol. Sci., 2007, 104(4), 374-383.
Na, H.K.; Kim, E.H.; Choi, M.A.; Park, J.M.; Kim, D.H.; Surh, Y.J. Diallyl trisulfide induces apoptosis in human breast cancer cells through ROS-mediated activation of JNK and AP-1. Biochem. Pharmacol., 2012, 84(10), 1241-1250.
Chandra-Kuntal, K.; Singh, S.V. 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.), 2010, 3(11), 1473-1483.
Shrotriya, S.; Kundu, J.K.; Na, H.K.; Surh, Y.J. 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., 2010, 70(5), 1932-1940.
Jakubikova, J.; Sedlak, J. Garlic-derived organosulfides induce cytotoxicity, apoptosis, cell cycle arrest and oxidative stress in human colon carcinoma cell lines. Neoplasma, 2006, 53(3), 191-199.
Bagul, M.; Kakumanu, S.; Wilson, T.A. Crude garlic extract inhibits cell proliferation and induces cell cycle arrest and apoptosis of cancer cells in vitro. J. Med. Food, 2015, 18(7), 731-737.
Arunkumar, A.; Vijayababu, M.R.; Srinivasan, N.; Aruldhas, M.M.; Arunakaran, J. Garlic compound, diallyl disulfide induces cell cycle arrest in prostate cancer cell line PC-3. Mol. Cell. Biochem., 2006, 288(1-2), 107-113.
Ling, H.; Lu, L.F.; He, J.; Xiao, G.H.; Jiang, H.; Su, Q. Diallyl disulfide selectively causes checkpoint kinase-1 mediated G2/M arrest in human MGC803 gastric cancer cell line. Oncol. Rep., 2014, 32(5), 2274-2282.
Tao, M.; Gao, L.; Pan, J.; Wang, X. Study on the inhibitory effect of allicin on human gastric cancer cell line SGC-7901 and its mechanism. Afr. J. Tradit. Complement. Altern. Med., 2014, 11(1), 176-179.
Dasgupta, P.; Bandyopadhyay, S.S. 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, 2013, 65(4), 611-622.
De Martino, A.; Filomeni, G.; Aquilano, K.; Ciriolo, M.R.; Rotilio, G. Effects of water garlic extracts on cell cycle and viability of HepG2 hepatoma cells. J. Nutr. Biochem., 2006, 17(11), 742-749.
Altonsy, M.O.; Andrews, S.C. Diallyl disulphide, a beneficial component of garlic oil, causes a redistribution of cell-cycle growth phases, induces apoptosis, and enhances butyrate-induced apoptosis in colorectal adenocarcinoma cells (HT-29). Nutr. Cancer, 2011, 63(7), 1104-1113.
Arunkumar, R.; Sharmila, G.; Elumalai, P.; Senthilkumar, K.; Banudevi, S.; Gunadharini, D.N.; Benson, C.S.; Daisy, P.; Arunakaran, J. Effect of diallyl disulfide on insulin-like growth factor signaling molecules involved in cell survival and proliferation of human prostate cancer cells in vitro and in silico approach through docking analysis. Phytomedicine, 2012, 19(10), 912-923.
Sung, J.; Harfouche, Y.; De La Cruz, M.; Zamora, M.P.; Liu, Y.; Rego, J.A.; Buckley, N.E. Garlic (Allium sativum) stimulates lipopolysaccharide-induced tumor necrosis factor-alpha production from J774A.1 murine macrophages. Phytother. Res., 2015, 29(2), 288-294.
Huang, L.; Song, Y.; Lian, J.; Wang, Z. Allicin inhibits the invasion of lung adenocarcinoma cells by altering tissue inhibitor of metalloproteinase/matrix metalloproteinase balance via reducing the activity of phosphoinositide 3-kinase/AKT signaling. Oncol. Lett., 2017, 14(1), 468-474.
Qian, Y.Q.; Feng, Z.H.; Li, X.B.; Hu, Z.C.; Xuan, J.W.; Wang, X.Y.; Xu, H.C.; Chen, J.X. Downregulating PI3K/Akt/NF-kappaB signaling with allicin for ameliorating the progression of osteoarthritis: In vitro and vivo studies. Food Funct., 2018, 9(9), 4865-4875.
Xiang, Y.; Zhao, J.; Zhao, M.; Wang, K. Allicin activates autophagic cell death to alleviate the malignant development of thyroid cancer. Exp. Ther. Med., 2018, 15(4), 3537-3543.
Wang, G.; Liu, G.; Ye, Y.; Fu, Y.; Zhang, X. Upregulation of miR-34a by diallyl disulfide suppresses invasion and induces apoptosis in SGC-7901 cells through inhibition of the PI3K/Akt signaling pathway. Oncol. Lett., 2016, 11(4), 2661-2667.
Yin, X.; Feng, C.; Han, L.; Ma, Y.; Jiao, Y.; Wang, J.; Jia, L.; Jing, F.; Gao, X.; Zhang, Y.; Zhang, J. Diallyl disulfide inhibits the metastasis of type esophagealgastric junction adenocarcinoma cells via NF-kappaB and PI3K/AKT signaling pathways in vitro. Oncol. Rep., 2018, 39(2), 784-794.
Shin, D.Y.; Kim, G.Y.; Lee, J.H.; Choi, B.T.; Yoo, Y.H.
Choi, Y.H. Apoptosis induction of human prostate carcinoma DU145 cells by diallyl disulfide via modulation of JNK and PI3K/AKT signaling pathways. Int. J. Mol. Sci., 2012, 13(11), 14158-14171.
Liu, Y.; Zhu, P.; Wang, Y.; Wei, Z.; Tao, L.; Zhu, Z.; Sheng, X.; Wang, S.; Ruan, J.; Liu, Z.; Cao, Y.; Shan, Y.; Sun, L.; Wang, A.; Chen, W.; Lu, Y. Antimetastatic therapies of the polysulfide diallyl trisulfide against triple-negative breast cancer (TNBC) via suppressing MMP2/9 by blocking NF-kappaB and ERK/MAPK signaling pathways. PLoS One, 2015, 10(4)e0123781
Kalra, N.; Arora, A.; Shukla, Y. Involvement of multiple signaling pathways in diallyl sulfide mediated apoptosis in mouse skin tumors. Asian Pac. J. Cancer Prev., 2006, 7(4), 556-562.
Xiao, D.; Lew, K.L.; Kim, Y.A.; Zeng, Y.; Hahm, E.R.; Dhir, R.; Singh, S.V. Diallyl trisulfide suppresses growth of PC-3 human prostate cancer xenograft in vivo in association with Bax and Bak induction. Clin. Cancer Res., 2006, 12(22), 6836-6843.
Huang, J.; Yang, B.; Xiang, T.; Peng, W.; Qiu, Z.; Wan, J.; Zhang, L.; Li, H.; Li, H.; Ren, G. Diallyl disulfide inhibits growth and metastatic potential of human triple-negative breast cancer cells through inactivation of the beta-catenin signaling pathway. Mol. Nutr. Food Res., 2015, 59(6), 1063-1075.
Zhang, Q.; Li, X.T.; Chen, Y.; Chen, J.Q.; Zhu, J.Y.; Meng, Y.; Wang, X.Q.; Li, Y.; Geng, S.S.; Xie, C.F.; Wu, J.S.; Zhong, C.Y.; Han, H.Y. Wnt/beta-catenin signaling mediates the suppressive effects of diallyl trisulfide on colorectal cancer stem cells. Cancer Chemother. Pharmacol., 2018, 81(6), 969-977.
Yin, X.; Zhang, J.; Li, X.; Liu, D.; Feng, C.; Liang, R.; Zhuang, K.; Cai, C.; Xue, X.; Jing, F.; Wang, X.; Wang, J.; Liu, X.; Ma, H. DADS suppresses human esophageal xenograft tumors through RAF/MEK/ERK and mitochondria-dependent pathways. Int. J. Mol. Sci., 2014, 15(7), 12422-12441.
Tan, H.; Ling, H.; He, J.; Yi, L.; Zhou, J.; Lin, M.; Su, Q. Inhibition of ERK and activation of p38 are involved in diallyl disulfide induced apoptosis of leukemia HL-60 cells. Arch. Pharm. Res., 2008, 31(6), 786-793.
Rahmani, A.H.; Alzohairy, M.A.; Khan, M.A.; Aly, S.M. Therapeutic implications of black seed and its constituent thymoquinone in the prevention of cancer through inactivation and activation of molecular pathways. Evid. Based Complement. Alternat. Med., 2014, 2014724658
Kelkel, M.; Cerella, C.; Mack, F.; Schneider, T.; Jacob, C.; Schumacher, M.; Dicato, M.; Diederich, M. ROS-independent JNK activation and multisite phosphorylation of Bcl-2 link diallyl tetrasulfide-induced mitotic arrest to apoptosis. Carcinogenesis, 2012, 33(11), 2162-2171.
Jiang, X.Y.; Zhu, X.S.; Xu, H.Y.; Zhao, Z.X.; Li, S.Y.; Li, S.Z.; Cai, J.H.; Cao, J.M. Diallyl trisulfide suppresses tumor growth through the attenuation of Nrf2/Akt and activation of p38/JNK and potentiates cisplatin efficacy in gastric cancer treatment. Acta Pharmacol. Sin., 2017, 38(7), 1048-1058.
Son, E.W.; Mo, S.J.; Rhee, D.K.; Pyo, S. 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., 2006, 6(12), 1788-1795.
Wang, W.; Cheng, J.; Zhu, Y. The JNK signaling pathway is a novel molecular target for S-propargyl- L-cysteine, a naturally-occurring garlic derivatives: Link to its anticancer activity in pancreatic cancer in vitro and in vivo. Curr. Cancer Drug Targets, 2015, 15(7), 613-623.
Lai, K.C.; Hsu, S.C.; Kuo, C.L.; Yang, J.S.; Ma, C.Y.; Lu, H.F.; Tang, N.Y.; Hsia, T.C.; Ho, H.C.; Chung, J.G. 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., 2013, 28(9), 479-488.
Sun, Y.; Liu, W.Z.; Liu, T.; Feng, X.; Yang, N.; Zhou, H.F. Signaling pathway of MAPK/ERK in cell proliferation, differentiation, migration, senescence and apoptosis. J. Recept. Signal Transduct. Res., 2015, 35(6), 600-604.
Chiba, T.; Soeno, Y.; Shirako, Y.; Sudo, H.; Yagishita, H.; Taya, Y.; Kawashiri, S.; Okada, Y.; Imai, K. MALT1 inhibition of oral carcinoma cell invasion and ERK/MAPK activation. J. Dent. Res., 2016, 95(4), 446-452.
Elango, E.M.; Asita, H.; Nidhi, G.; Seema, P.; Banerji, A.; Kuriakose, M.A. Inhibition of cyclooxygenase-2 by diallyl sulfides (DAS) in HEK 293T cells. J. Appl. Genet., 2004, 45(4), 469-471.
Shin, D.Y.; Cha, H.J.; Kim, G.Y.; Kim, W.J.; Choi, Y.H. Inhibiting invasion into human bladder carcinoma 5637 cells with diallyl trisulfide by inhibiting matrix metalloproteinase activities and tightening tight junctions. Int. J. Mol. Sci., 2013, 14(10), 19911-19922.
Park, H.S.; Kim, G.Y.; Choi, I.W.; Kim, N.D.; Hwang, H.J.; Choi, Y.W.; Choi, Y.H. Inhibition of matrix metalloproteinase activities and tightening of tight junctions by diallyl disulfide in AGS human gastric carcinoma cells. J. Food Sci., 2011, 76(4), T105-T111.
Dasgupta, P.; Sengupta, S.B. Role of diallyl disulfide-mediated cleavage of c-Myc and Sp-1 in the regulation of telomerase activity in human lymphoma cell line U937. Nutrition, 2015, 31(7-8), 1031-1037.
Sun, L.; Wang, X. Effects of allicin on both telomerase activity and apoptosis in gastric cancer SGC-7901 cells. World J. Gastroenterol., 2003, 9(9), 1930-1934.
Pagliei, B.; Aquilano, K.; Baldelli, S.; Ciriolo, M.R. Garlic-derived diallyl disulfide modulates peroxisome proliferator activated receptor gamma co-activator 1 alpha in neuroblastoma cells. Biochem. Pharmacol., 2013, 85(3), 335-344.
Jana, S.; Mandlekar, S. Role of phase II drug metabolizing enzymes in cancer chemoprevention. Curr. Drug Metab., 2009, 10(6), 595-616.
Tsai, C.W.; Yang, J.J.; Chen, H.W.; Sheen, L.Y.; Lii, C.K. Garlic organosulfur compounds upregulate the expression of the pi class of glutathione S-transferase in rat primary hepatocytes. J. Nutr., 2005, 135(11), 2560-2565.
Chen, C.; Pung, D.; Leong, V.; Hebbar, V.; Shen, G.; Nair, S.; Li, W.; Kong, A.N. Induction of detoxifying enzymes by garlic organosulfur compounds through transcription factor Nrf2: Effect of chemical structure and stress signals. Free Radic. Biol. Med., 2004, 37(10), 1578-1590.
Rana, S.V.; Pal, R.; Vaiphei, K.; Singh, K. Garlic hepatotoxicity: Safe dose of garlic. Trop. Gastroenterol., 2006, 27(1), 26-30.
Adeola, F.; Enaibe, B.; Avwioro, G. Evaluating toxicity profile of garlic (Allium sativum) on the liver, kidney and heart using wistar rat model. Int. J. Trop. Dis. Health, 2017, 26, 1-12.
Cheng, K.K.; Yeung, C.F.; Ho, S.W.; Chow, S.F.; Chow, A.H.; Baum, L. Highly stabilized curcumin nanoparticles tested in an in vitro blood-brain barrier model and in Alzheimer’s disease Tg2576 mice. AAPS J., 2013, 15(2), 324-336.
Khan, A.; Shukla, Y.; Kalra, N.; Alam, M.; Ahmad, M.G.; Hakim, S.R.; Owais, M. Potential of diallyl sulfide bearing pH-sensitive liposomes in chemoprevention against DMBA-induced skin papilloma. Mol. Med., 2007, 13(7-8), 443-451.
Maroof, A.; Farazuddin, M.; Owais, M. Potential use of liposomal diallyl sulfide in the treatment of experimental murine candidiasis. Biosci. Rep., 2010, 30(4), 223-231.
Dasgupta, P.; Bhattacharya, A.; Pal, R.; Dasgupta, A.K.; Sengupta, S. Synthesis of diallyl disulfide (DADS) induced gold nanoparticles: Characterization and study of its biological activity in human leukemic cell-lines. RSC Advances, 2015, 5(24), 18429-18437.

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy