TABLE 2.
Potential antineoplastic effects of DADS and its underlying mechanisms based on in vivo studies.
| Animal tumor models | Anticancer effects | Mechanisms | Dose (route) | Duration | References |
|---|---|---|---|---|---|
| Breast cancer | |||||
| Female athymic mice (breast) | Retarded the tumor growth | Not reported | Intraperitoneal injection (1 or 2 mg) 3 times a week | 35 days | Tsubura et al. (2012) |
| Ehrlich ascites carcinoma (EAC) bearing female albino mice | Modulated apoptosis | ↑Apoptosis, ↓Bcl-2, ↑p53, ↑deoxynucleotidyl transferase, ↓sialic acid | Intraperitoneally 100 mg/kg | 2 weeks | Ahmed and Ahmed, (2015) |
| Esophageal cancer | |||||
| ECA109 injected nude mice | Induced apoptosis | ↓PCNA, ↓RAF/MEK/ERK, ↑caspase-3, ↑p53, ↑Bax/Bcl-2 ratio | 20 and 40 mg/kg (i.p.) | 24 h | Yin et al. (2014a) |
| Gastric cancer | |||||
| Male Balb/c nude mice | Induced apoptosis | ↑miR-22, ↑miR-200b | 100 mg kg−1 (s.c.) | 48 h | Tang et al. (2013) |
| MGC803 injected nude mice | Inhibited cell invasion | ↓ p-cofilin1, ↓Rac1-Pak1/Rock1-LIMK1 pathway, ↓EMT, ↓p-LIMK1, ↓MMP-9, ↑ TIMP-3 | 30 mg/L (s.c.) | 12, 24, and 48 h | Bo et al. (2016) |
| MGC803 injected male athymic BALB/c nude mice | Exerted anti-EMT and antitumor growth effects | ↓Ki-67, ↓CD34, ↓vimentin, ↑E-cadherin | 30 mg/L (s.c.) | 0.12, 24 and 48 h | Su et al. (2018) |
| MGC803 -xenografted nude mice | Arrested cell cycle and inhibited cell proliferation | ↑Acetylated histones H3 and H4, ↑p21WAF1 protein expression | 50, 100, and 200 mg/kg (s.c.) | 0, 6, 12, or 24 h | Su, (2012) |
| Colon cancer | |||||
| Colo 205 xenograft mice | Elevated chemo-resistance of human cancer cells | ↑Mdr1, MRP1, MRP3, MRP4 and MRP6 gene expression | 25 μM (s.c.) | 24-h and 48-h | Lai et al. (2012) |
| FVB/N mice | Prevented colorectal tumorigenesis | ↓prolonged inflammation and cellular transformation; ↓GSK-3β, ↓NF-κB | 10 mg/kg (i.p.) | 24 h | Saud et al. (2016) |
| SW480 injected nude mice | Inhibited proliferation and arrested cell cycle | ↓PCNA, ↓p53, ↓cyclin B1, ↑p21WAF1 | 30 mg/kg (s.c.) | 24 h | Liao et al. (2007) |
| SW620, SW480, and HCT116 injected nude mice | Inhibited migration and invasion | ↓Rac1, ↓N-cadherin, ↓vimentin, ↓snail1, ↑E-cadherin | 1.008 g/ml (i.v.) | 24 h | Xia et al. (2019) |
| HCT116, DLD-1, HT29, and SW620 injected BALB/c nude mice | Initiated apoptosis | ↓Bcl-2, ↑Bak, ↑Bax, ↑caspase-9 | 100 µL (s.c.) | 24 h | Kim et al. (2019) |
| SW480 injected nude mice | Inhibited the migration and invasion | ↓phosphorylation of ADF/cofilin, ↓LIMK1, ↓vimentin, ↓CD34, ↓ Ki-67 | 45 mg/L (s.c.) | 24 h | Su et al. (2017) |
| Caco-2,HT-29 injected rodents | Increased histone acetylation and provided protective properties | ↑p21waf1/cip1 expression, ↑histone H3 acetylation, ↑histone H4 hyperacetylation, ↓HDAC activity, ↓AM at the same | 200 µM (s.c.) | 6 h | Druesne et al. (2004) |
| Caco-2, HT-29 injected colonocytes | Increased histone acetylation and cell cycle arrest | ↑CDKN1A promoter-associated histone acetylation, ↑p21cip1 mRNA and protein levels | 200 mg/kg (Intracaecal perfusion and gavage) | 1 and 21 h | Druesne-Pecollo et al. (2008) |
| Hepatocellular cancer | |||||
| Thirty male Sprague-Dawley rats | Induced antioxidant defense mechanism and reduced inflammatory response | ↓NF-ĸB translocation, ↓ IĸBα phosphorylation, ↑Bax, ↑cytochrome c, ↑caspase-3, ↑Nrf2 translocation, ↑phase II/antioxidant enzyme activities | 50 and 100 mg/kg/day (gavaged) | 5 days | Lee et al. (2014) |
| Twenty four healthy male rats | Provided protective effects | ↓hepatic CYP2E1 expression, ↓NF-κB activation, ↓serum AST and ALT levels, ↓MDA, ↓JNK activation, ↑GSH, ↑antioxidant enzymes activities | 100 mg/kg/day (oral gavage) | 5 days | Ko et al. (2017) |
| c57Bl/6J mice | Effectively attenuated hepatic steatosis, lipotoxicity, lipid peroxidation and inflammation | ↓serum AST and ALT levels, ↓liver TG and TC contents, ↓ mRNA levels of SREBP-1 and Apoa-I, ↓SCD-1, ↓ NF-κB, ↓ TNF-α, ↓IL-6, ↓MDA, ↓SOD, ↑PPARα, ↑mRNA levels of CREBH and FGF21 | 20, 50, and 100 mg/kg (s.c.) | 4 or 20 weeks | Zhang et al. (2019a) |
| CP feeded male adult albino rats | Reduced hepatotoxicity | ↑ALT, ↑AST, ↑ALP, ↑ total and direct bilirubin levels, ↑γ-GT, ↑HDL-C, ↑GPx, ↓serum cholesterol, ↓ triglycerides, ↑CAT, ↓LDL-C, ↓ VLDL-C levels, ↓MDA, ↓PCC, ↓NOX-4 | 200 mg/kg (oral) | 10 days | Hasan et al. (2020) |
| CRL1439 treated rats | Triggered apoptosis | ↓IGF-1R, ↓Fas/TNFRSF6/APO | 150 µM (oral) | 2 h | Odewumi et al. (2019) |
| Leukemia | |||||
| HL-60 injected mice | Inhibited proliferation, migration, invasion and arrested cells at G0/G1 stage | ↑differentiation, ↑ CD11b expression, ↓NBT, ↓DJ-1, ↓ cofilin 1, ↓RhoGDI2, ↓CTR, ↓PCNA | 21, 42 and 84 mg/kg (s.c.) | 5 days | Ling et al. (2017) |
| HL-60 injected SCID mice | Reduced cell proliferation, invasion, and differentiation | ↓CRT, ↓CD33, ↑C/EBPα, ↑ROS | 21 or 42 mg/kg (s.c.) | 21 days | Sun et al. (2019) |
| Skin cancer | |||||
| DMBA/TPA-treated mouse | Inhibited chemically induced papilloma genesis | ↑CAT, ↑SOD, ↑GPx, ↑GR, ↑nuclear accumulation of Nrf2 | 4 µM (topical) | 4 days | Shan et al. (2016) |