TABLE 1.
Summary of mechanisms of allicin and its secondary metabolites against cancers of digestive system.
| Cancer | Intervention reagent | Dose(s) | Effects | Type of research | Animal model | Cell lines | References |
|---|---|---|---|---|---|---|---|
| Gastric cancer | Allicin | NA | Increase Bax and Fas expression, and decrease Bcl-2 expression level | Clinical trial | NA | NA | Zhang et al. (2008) |
| Allicin | 3, 6, 9, and 12 μg/ml | Induce gastric cancer cell stagnation at M stage and up-regulated p21WAF1 and p16INK4 genes | In vitro | NA | MGC-803 and SGC-7901 | Ha and Yuan, (2004) | |
| Allicin | 3, 6, and 12 mg/L | Arrest the G2/M phase, inhibited cell proliferation and induced apoptosis | In vitro | NA | SGC-7901 | Tao et al. (2014) | |
| Allicin | 15–120 μg/ml | Simultaneously active intrinsic mitochondrial and extrinsic Fas/FasL-mediated pathways of apoptosis, induce cytochrome C release from the mitochondria, increase caspase-3, -8, and -9 activation, upregulate Bax and Fas expression in the tumor cells | In vitro | NA | SGC-7901 | Zhang et al. (2010) | |
| Allicin | 0.1, 0.05, and 0.016 mg/ml | Inhibit telomerase activity and induce apoptosis | In vitro | NA | SGC-7901 | Sun and Wang, (2003) | |
| Allicin | 0.1, 1, and 10 μg/ml | Induce apoptosis through the P38-MAPK/caspase-3 signaling pathway | In vitro | NA | MGC-803, BGC-823 and SGC-7901 cell | Zhang et al. (2015) | |
| ABGE | In vivo: 0, 200, 400, 800 mg/kg, intraperitoneally, for 2 weeks; in vitro: 0, 10, 50, and 100 mg/ml | Induce apoptsis of cancer cells and inhibit the growth of tumor | In vivo and in vitro | Tumor-bearing mice model | SGC-7901 | Wang et al. (2012) | |
| DATS | In vivo: 20, 30 and 40 mg/kg; in vitro: 0, 25, 50, 100, 200, 400 µM | Decrease G1 phase, increase G2/M phase, induce apoptosis by down-regulating Bcl-2 and activating MAPK and affecting PI3K/AKT pathways, increase levels of IL-12, IFN-γ and TNF-α level in the host, suppress tumor invasion and metastasis | In vivo and in vitro | SGC-7901 xenograft mice model | SGC-7901 | Jiang et al. (2017b) | |
| DATS | In vivo: 20, 30 and 40 mg/kg; in vitro: 50, 100, and 200 μmol/L | Induce G2/M phase cell cycle arrest, down-regulate Bcl-2 as well as up-regulate Bax, P53 and cytochrome C, induce apoptosis through activation of the caspase pathway, attenuate Nrf2/Akt and activative of the JNK and P38-MAPK pathways, and improve the anti-tumor efficacy of cisplatin (DDP) | In vivo and in vitro | BALB/c nude mice BGC-823 xenograft model | BGC-823 | Jiang et al. (2017a) | |
| Colorectal cancer | Allicin | In the mouse model: 48 mg/kg to achieve 5 g/day; in HCT-116 cells: 25 µM for 24 h | Prevent tumorigenesis by inhibiting the STAT3 signaling pathway activation | In vivo and in vitro | AOM/DSS model of colorectal cancer mouse model | HCT-116 | Li et al. (2019b) |
| Allicin | 0, 2, 4, 8, 16, 32, 64, 128 and 256 μg/ml | Improve the radiosensitivity of colorectal cancer cells by inhibiting NF-κB signaling pathway | In vivo and in vitro | Transplantation of CT26 cell in BALB/c mice | HCT-116,CT26 | Huang et al. (2020) | |
| Allicin | 10–25 µM | Transiently deplete the intracellular GSH level, and inhibit the proliferation of cancer cells | In vitro | NA | HT-29 | Hirsch et al. (2000) | |
| Allicin | 0–1.2 mM | Reduce cell viability and cell proliferation | In vitro | NA | HT-29 | Gruhlke et al. (2016) | |
| Allicin | 1–50 μg/ml for 24, 48, and 72 h | Induce apoptotic death via Nrf2, enhance hypodiploid DNA content, decrease Bcl-2, increase Bax and capability of releasing cytochrome C from mitochondria to cytosol | In vitro | NA | HCT-116, LS174T, HT-29, and Caco-2 | Bat-Chen et al. (2010) | |
| Allicin | 3 and 6 μg/ml | Inhibit invasion and metastasis at non-cytotoxic concentration via down-regulating the expression of VEGF, u-PAR and HPA mRNA | In vitro | NA | LoVo | Gao et al. (2009b) | |
| Allicin | 4 and 8 mg/L | Inhibit cancer cells proliferation by induction of apoptosis and arrestment of cell cycle, and enhancing the cytotoxicity of CPT-11 | In vitro | NA | LoVo | Gao et al. (2009a) | |
| Allicin | 1.625, 3.125, 6.25, 12.5, 25, 50, and100 µM | 5-FU combined with allicin has a synergistic effect against colon cancer cells, and better results can be obtained than the single-agent treatment at IC50 with a lower concentration of 5-FU. | In vitro | NA | DLD-1 | Țigu et al. (2020) | |
| Allicin | 2.5, 5, 10, 25, 50, 75, and 100 μg/ml | Enhanced the effects of 5-FU and oxaliplatin against cancer cells | In vitro | NA | Caco-2 and HT-29 | Perez-Ortiz et al. (2020) | |
| ABGE | 0, 20, 50, and 100 mg/ml | Inhibit the growth and induced apoptosis in HT29 cells via inhibiting of the PI3K/Akt pathway | In vitro | NA | HT-29 | Dong et al. (2014) | |
| AGE | Active treatment: high-dose AGE 2.4 ml/d; controlled group: low-dose AGE 0.16 ml/d | AGE can reduce the occurrence and growth and spread of colorectal adenomas | Clinical trial | NA | NA | Tanaka et al. (2006) | |
| AGE | 0, 0.1, 1, and 10 mg/ml | Inhibit proliferation and angiogenesis through the suppression of endothelial cell motility, proliferation, and tube formation | In vitro | NA | HT-29, SW480, and SW620 | Matsuura et al. (2006) | |
| AGE | In vivo: a basal diet containing 3% wt/wt AGE; in vitro: 0, 1, 5, or 10 mg/ml AGE | Suppress the proliferative activity in adenoma and adenocarcinoma lesions, without effect on normal colon mucosa, delay cell cycle progression by downregulating cyclin B1 and cdk1 expression via inactivation of NF-κB but did not induce apoptosis | In vivo and in vitro | F344 rats with DMH-induced colon carcinogenesis | DLD-1 | Jikihara et al. (2015) | |
| CGE | 0.125, 0.25, 0.5, or 1 μg/ml | Inhibit proliferation, induces arrest of cell cycle and apoptosis | In vitro | NA | Caco-2 | Bagul et al. (2015) | |
| DADS | 62.5, 125, 250, 500, and 1,000 ppm | Increase activities of phase II enzymes such as GST, NAD(P)H-dependent quinone reductase, and UDP-glucuronosyl transferase in the liver and colon | In vivo | AOM-induced colon caicinogenesis in male F344 rats | NA | Reddy et al. (1993) | |
| DADS | 1 mg thrice weekly; 0.5 mg thrice weekly | Reduce the toxicity of 5-FU and inhibit the growth of human colon tumor cell xenografts | In vivo | NCr nu/nu mice xenotransplanted colon cancer cell line HCT-15 | HCT-15 | Sundaram and Milner, (1996) | |
| DADS | 85 ppm of DADS (60 mg daily human equivalent dose) in the diet | Inactivate NF-κB and prevent colitis-induced colorectal cancer by inhibiting GSK-3β | In vivo | FVB/N mice treated with AOM/DSS | NA | Saud et al. (2016) | |
| DAS | 200 mg/kg | Reduce the incidence rate of colorectal adenocarcinoma | In vivo | C57BL/6J mice with DMH-induced colorectal cancer | NA | Wargovich, (1987) | |
| DATS | 1–100 µM | Suppress the proliferation and induces apoptosis through oxidative modification of β-tubulin | In vivo and in vitro | Nude mice model bearing HCT-15 xenografts | HCT-15 and DLD-1 | Hosono et al. (2005) | |
| SAMC | 0–450 µM | Inhibit cell proliferation and induce apoptosis via the JNK and P38 pathways | In vitro | NA | SW620 | Zhang et al. (2014) | |
| Z-ajoene | 0, 10, and 30 µM | Inhibit growth of colon cancer cells by promotion of CK1α dependent β-catenin phosphorylation | In vitro | NA | SW480 | Li et al. (2020b) | |
| Liver cancer | Allicin | In vivo: 5 mg/kg/day, every 2 days for 3 weeks; SK-Hep-1 cells: 0, 1, 2, 4, 8,10, 16, 20, 32, 40, and 64 μg/ml; BEL -7402: 0, 1.25, 2.5, 5, 10, 20, 40, 80,and 160 μg/ml | Promote anti-tumor activity of 5-FU through ROS-mediated mitochondrial pathway | In vivo and in vitro | HCC xenograft tumors in nude mice | SK-Hep-1 and BEL-7402 | Zou et al. (2016) |
| Allicin | 0, 15, 20, 25, 35, 40, and 50 µM | Induce apoptosis through caspase-dependent and caspase-independent pathways by ROS overproduction | In vitro | NA | Hep G2 and Hep 3B | Chu et al. (2012) | |
| Allicin | 35 µM | Induce P53-mediated autophagy, decrease cytoplasmic P53, the PI3K/mTOR signaling, and the level of Bcl-2, increase the expression of AMPK/TSC2 and Beclin-1 | In vitro | NA | Hep G2 | Chu et al. (2013) | |
| Allicin | 5–100 μM | Reduce the aflatoxin B1 genotoxicity in Hep G2 cells | In vitro | NA | Hep G2 | Belloir et al. (2006) | |
| SAC | In vivo: 1 mg/kg/day; in vitro: 0–40 mM | Suppress proliferation and metastasis of hepatocellular carcinoma | In vivo and in vitro | Orthotopic xenograft liver tumor model | MHCC97L | Ng et al. (2012) | |
| SAC | 5–100 μM | Reduce the aflatoxin B1 genotoxicity and the DNA damage induced by DMN in Hep G2 cells | In vitro | NA | Hep G2 | Belloir et al. (2006) | |
| AGE | 500 mg/day | Prevent a decline of NK cell number and activity in patients with advanced cancer | Clinical trial | NA | NA | Ishikawa et al. (2006) | |
| AGE | 5% w/v, 0.5 ml daily | Against hepatotoxicity, oxidative stress and the hepatocarcinoma induced by p-dimethylaminoazobenzene and phenobarbital in the experimental rats | In vivo | Rattus norvegicus fed chronically with two liver carcinogens, p-dimethylaminoazobenzene and phenobarbital to produce hepatotoxicity | NA | Pathak et al. (2020) | |
| Alliin | NA | Reduce DNA damage induced by NDMA in liver | In vitro | DNA damage induced by NDMA in SPF rat liver | NA | Singh et al. (2006) | |
| AM | 5–100 μM | Decrease the DNA damage induced by DMN in Hep G2 cells | In vitro | NA | Hep G2 | Belloir et al. (2006) | |
| DADS | 5–100 μM | Reduce the aflatoxin B1 genotoxicity and benzo(a)pyrene genotoxicity in Hep G2 cells | In vitro | NA | Hep G2 | Belloir et al. (2006) | |
| DADS | 100 μmol/L | Induced apoptosis through P38-MAPK and caspase-3 | In vitro | NA | Hep G2 | Ji et al. (2010) | |
| DAS | 5–100 μM | Reduce the aflatoxin B1 genotoxicity, and show a low effect towards DMN genotoxicity in Hep G2 cells | In vitro | NA | Hep G2 | Belloir et al. (2006) | |
| SAMC | 300 mg/kg | Inhibit hepatocarcinogenesis through targeting LRP6/Wnt pathway | In vivo | Xenograft and orthotopic HCC nude mice model | HuH-7 | Xiao et al. (2018) | |
| Cholangiocarcinoma | Allicin | 0, 5, 10, 20, and 40 µM | Inhibit cell proliferation and invasion through STAT3 signaling | In vivo and in vitro | Nude mouse model of CCA | HuCCT-1 and QBC939 | Chen et al. (2018) |
| Esophageal cancer | DAS | 200 mg/kg | Inhibit the tumorigenic effects of potent, metabolically activated monoalkylating carcinogens in the gastrointestinal tract | In vivo | DNA-damaging and tumorigenic effects induced by NMBA in rat esophagus | NA | Wargovich et al. (1988) |
| Ajoene | NA | Inhibit proliferation and induce apoptosis of human esophageal-cancer cells | In vitro | NA | WHCO1 | Kaschula et al. (2016) | |
| Ajoene analogue | 10 µM | Suppress cell proliferation, induce G2/M cell cycle arrest, and induce apoptosis via caspase-3 activation | In vitro | NA | WHCO1 | Kaschula et al. (2012) | |
| Ajoene analogue | NA | Induce cytotoxicity by activating the unfolded protein response via CHOP/GADD153 | In vitro | NA | WHCO1 | Siyo et al. (2017) | |
| Pancreatic cancer | Allicin | 10 mg/kg | Inhibit tumor growth and prolonged survival time | In vivo | C57/BL6 nude mice pancreatic cancer xenograft model | BXPC-3 | Wang et al. (2013) |
| DATS | 100 μmol/L | Induces apoptosis of pancreatic tumorigenic cells and ductal epithelial cells | In vitro | NA | Capan-2, and H6C7 | Ma et al. (2014) | |
| Garlic oil | 2.5 and 10 µM | Induce pro-apoptosis effects on AsPC-1 cells in a dose- and time-dependent manner | In vitro | NA | AsPC-1, PANC-1, and Mia PaCa-2 | Lan et al. (2013) |