Table 2.
Potential antineoplastic effects and underlying mechanisms of action of SFN based on in vivo studies.
| Animal Tumor Models | Anticancer Effects | Mechanisms | Dose (Route) |
Duration | References |
|---|---|---|---|---|---|
| Breast cancer | |||||
| BALB/c mice injected with F3II cells | Suppressed tumor development | ↓PCNA; ↑PARP fragment | 15 nmol, daily (i.v.) |
13 days | Jackson and Singletary, 2004 [95] |
| Nude female BALB/c mice xenografted with MDA-MB-231-Luc-D3H1 cells | Inhibited tumor growth | ↓ALDH1A1; ↓NANOG; ↓CR1; ↓GDF3; ↓FOXD3; ↓NOTCH4; ↓WNT3 | 50 mg/kg (i.p.) |
3, 5 weeks | Castro et al., 2019 [86] |
| Female athymic BALB/c mice transplanted with KPL-1 cells | Suppressed tumor growth | ↑Apoptotic ratio | 25, 50 mg/kg (i.p.) |
26 days | Kanematsu et al., 2011 [265] |
| Nude mice xenografted with MDA-MB-453 cells | Reduced tumor size | ↑Egr1; ↓cyclin B1; ↓CDC25c | 100 mg/kg (i.v.) |
15 days | Yang et al., 2016 [106] |
| Gastrointestinal tract and associated cancers | |||||
| Esophageal cancer | |||||
| SCID mice inoculated with BEAC and FLO-1 cells | Reduced tumor size | Not reported | 0.75 mg/day (s.c.) |
2 weeks | Qazi et al., 2010 [121] |
| Male BALB/c mice inoculated with ECa109 cells | Decreased tumor size | ↑LC3B-II; ↓P62 | 5 mg/kg, every other day (i.p.) | 2 weeks | Lu et al., 2020 [122] |
| Small intestine | |||||
| Male ApcMin/+ mice | Decreased tumor number and size | ↑Apoptosis; ↓p-JNK; ↓p-ERK; ↓p-Akt | 300 and 600 ppm/day (via diet) |
3 weeks | Hu et al., 2006 [266] |
| Male ApcMin/+ mice | Reduced tumor size | ↑Apoptosis; ↑p21; ↑caspase-3; ↑caspase-9; ↑COX-2; ↓p-Akt | 300 and 600 ppm/day (via diet) |
3, 10 weeks | Shen et al., 2007 [267] |
| Colon cancer | |||||
| Nude male mice xenografted with HCT116 cells | Suppressed tumor growth; decreased tumor size | ↑CDK1; ↑MK2; ↑p38 phosphorylation | 1 and 5 mg/kg/day (i.p.) |
13 days | Byun et al., 2016 [134] |
| Male C57BL/6J+/Min mice | Inhibited tumor growth | ↓HDAC; ↑acetylated histone H4; ↑p21; ↑Bax | ~6 µmol/day (via diet) |
10 weeks | Myzak et al., 2006 [245] |
| Male WT and Nrf2 mice induced tumors with DMT | Reduced tumor size | ↓HDAC; ↓HDAC3 protein; ↑global histone H4 acetylation | 400 ppm/day or alternate days (via diet) |
25, 35 weeks | Rajendran et al., 2015 [268] |
| Hepatocellular cancer | |||||
| Female BALB/c athymic mice inoculated with HepG2 cells | Reduced tumor growth and volume | Not reported | 50 mg/kg, every 2 days (i.p.) | 13 days | Wu et al., 2016 [160] |
| Pancreatic cancer | |||||
| Male Syrian Hamster injected with BOP to initiate carcinogenesis | Prevented pancreatic carcinogenesis | Not reported | 80 ppm/day (p.o.) | 3 weeks | Kuroiwa et al., 2006 [269] |
| Male SCID mice inoculated with PANC-1 | Decreased tumor growth | Not reported | 250–500 µmol/kg/d (i.p.) | 3 weeks | Pham et al., 2004 [163] |
| Female athymic (nu/nu) mice inoculated with Mia Paca-2 | Inhibited tumor growth | Not reported | 25 or 50 mg/kg (5× per week i.p.) | 4 weeks | Li et al., 2012 [164] |
| Male NOD/SCID/IL2Rγ mice inoculated with human pancreatic CSCs | Reduced tumor growth | ↓Smo; ↓Gli 1; ↓Gli 2; ↓Oct-4; ↓VEGF; ↓PDGFα; ↓Bcl-2; ↓XIAP; ↑E-Cadherin | 20 mg/kg/day (5× per week p.o.) |
6 weeks | Li et al., 2013 [270] |
| Nude mice inoculated with MIA-PaCa2 | Blocked tumor growth and angiogenesis | ↑Apoptosis; ↓NK-κB binding | 4.4 mg/kg (i.p.) on days 4, 5, and 6 after tumor transplant | 1 week | Kallifatidis et al., 2009 [165] |
| BALB/c nude mice (transgenic pancreatic cancer mice) | Reduced tumor volume and weight | ↑Nrf2; ↓Ki-67; ↑p-AMPK | 50 mg/kg, every other day (i.p.) |
120 days | Chen et al., 2018 [169] |
| Gynecological cancers | |||||
| Endometrial cancer | |||||
| Female SCID mice inoculated with Ishikawa cells | Reduced tumor volume | ↑Apoptosis | 50 mg/kg once a day (i.p.) | 30 days | Rai et al., 2020 [175] |
| Ovarian cancer | |||||
| Athymic mice inoculated with A2780 cells | Inhibited tumor growth | ↑IP3R | 40 mg/kg, once a day (i.p.) | 7 days | Hudecova et al., 2016 [180] |
| Lung cancer | |||||
| A/J mice treated with benzopyrene and NNK | Inhibited cellular proliferation. Reduced tumor size and weight | ↑Apoptosis; ↑casspase-3; ↓PCNA | 1.5 and 5 µmol/g (p.o.) |
42 weeks | Conaway et al., 2005 [271] |
| Nude mice inoculated with LTEP-A2 cells | Reduced tumor weight | ↑Apoptosis; ↑G2/M arrest | 25–100 mg/kg, 3 doses/week (i.p.) | 9 days | Liang et al., 2008 [194] |
| NOD/SCID mice inoculated with A549 cells | Reduced tumor volume and weight | ↑Apoptosis; ↑H3 acetylation, ↑H4 acetylation; ↑p53; ↑p21; ↑Bax; ↑G0/G1 arrest; ↑G2/M arrest; ↓HDAC | 9 µM/mice/day on alternate days (p.o.) |
28 days | Jiang et al., 2016 [197] |
| BALB/c nu/nu male mice inoculated with NSCLC | Reduced tumor volume | ↓EGFR | 10 µmol/kg, 5 doses/week (i.t.) |
21 days | Chen et al., 2015 [204] |
| BALB/c nude female inoculated with H1299 | Reduced tumor weight and volume and inhibited cell migration and invasion | ↑ERK5; ↑pERK5; ↑E-Cadherin; ↑ZO-1; ↓pc-jun; ↓pc-Fos; ↓N-Cadherin; ↓Snail1 | 25 and 50 mg/kg every 3 days (i.p.) | 21 days | Chen et al., 2019 [205] |
| Nude male BALB/c mice inoculated with H1299 and 95D cells | Decreased the incidence of lung metastasis | ↓miRNA-616-5p; ↓β-catenin; ↓N-cadherin; ↓Vimentin | 25 or 50 mg/kg, every 3 days (i.v.) |
4 weeks | Wang et al., 2017 [200] |
| Neurological cancer | |||||
| Female NSG mice inoculated with GBM10 cells | Inhibited tumor growth | Not reported | 100 mg/kg for 5-day cycles (p.o.) | 3 weeks | Bijangi-Visheshsaraei et al., 2017 [209] |
| Skin cancer | |||||
| C57BL/6 mice injected with B16F-10 melanoma cells | Inhibited tumor growth and lung metastasis | ↓Lung hydroxyproline; ↓lung uronic acid; ↓lung hexosamine; ↓serum sialic acid; ↓serum GGT; ↑IL-2; ↑IFN-γ; ↓IL-1β; ↓IL-6; ↓TNF-α | 500 µg/kg (i.p.) | 10 days | Thejass and Kuttan, 2006 [272]; Thejass and Kuttan, 2007 [273] |
| C57BL/6 mice inoculated with B16 cells | Reduced tumor volume | ↓HDAC | 500 µmol/kg, 3 doses/week (i.p.) |
4 weeks | Do et al., 2010 [218] |
| C57Bl/6 mice inoculated with B16 cells | Inhibited tumor growth and reduced volume | ↓HDAC | 500 µmol/kg, 3 doses/week (i.p.) |
4 weeks | Enriquez et al., 2013 [217] |
| NSG mice inoculated with A375 | Reduced tumor formation and volume | ↑Apoptosis; ↓Ezh2; ↓H3K27me3; ↓MMP-9; ↓MMP-2; ↑TIMP3; ↑PARP cleavage; ↑procaspase-8; ↑procaspase-9 |
10 µmol/kg, 3 doses/week (p.o.) |
6 weeks | Fisher et al., 2016 [215] |
| Urogenital cancers | |||||
| Bladder cancer | |||||
| Nude female athymic mice xenografted with UMUC3 cells | Inhibited tumor growth | Not reported | 295 µmol/kg (p.o.) |
2 weeks | Abbaoui et al., 2012 [82] |
| Male athymic mice xenografted with UMUC3 cells | Suppressed tumor growth | ↑Apoptosis; ↑caspase-3; ↑cyt. c; ↓survivin | 12 mg/kg (p.o.) |
5 weeks | Wang and Shan, 2012 [274] |
| Prostate cancer | |||||
| Nude male athymic BALB/c (nu/nu) mice xenografted with PC-3 cells | Reduced tumor growth | ↑Apoptosis; ↑Bax; ↑Ac-H3; ↑Ac-H4; ↓HDAC | 443 mg/kg/day (p.o.) |
3 weeks | Myzak et al., 2007 [84] |
| Male and female athymic mice PC-3 xenograft | Inhibited tumor growth | ↑Apoptosis; ↑Bax | 5.6 µmol, 3 times/week (p.o.) | 3 weeks | Singh et al., 2004 [240] |
| Male TRAMP [C57BL/6xFVB]F1 hybrid | Decreased cell proliferation and pulmonary metastasis | ↑Apoptosis; ↑E-Cadherin; ↑Bad; ↑Bak; ↑Bid; ↑Bax; ↑NK cell cytotoxicity; ↑PARP cleavage; ↓Mcl-1; ↑T-cell infiltration | 6 µmol, 3 times/week (p.o.) | 17–19 weeks | Singh et al., 2009 [275] |
| PTEN^ L/L;PB-Cre4 mice | Inhibited cell viability and proliferation | ↑Apoptosis; ↑cell cycle arrest; ↑caspase-3; ↑caspase-7; ↑cyclin B1; ↓cyclin D2 | 0.1, 1 µmol/g/day (p.o.) |
8 weeks | Traka et al., 2010 [276] |
| TRAMP mice | Inhibited tumor growth | ↓ACC1; ↓FASN; ↓acetyl-coA; ↓total FFA; ↓phospholipids | Not specified | Not specified | Singh et al., 2018 [262] |
| TRAMP and Hi-Myc mice with prostate adenocarcinoma | Decreased tumor size | ↓Glycolysis; ↓HKII; ↓PKM2; ↓LDHA; ↓lactate | 1 mg, 3 times/week (p.o.) | 5 weeks | Singh et al., 2019 [253] |
Symbols: ↑, increased or upregulated; ↓decreased or downregulated.