Table 1.
In vivo anti-cancer effects of resveratrol.
| Cancer Model | Animal Model | Dose | Outcome | References |
|---|---|---|---|---|
| Skin | DMBA/TPA model in female CD-1 mice | 1, 5, 10, 25 μmol topically twice/week for 18 weeks | Incidence↓ Number of tumors per mouse↓ | [46] |
| Mouse xenograft models of A431 cells | 10, 20, 40 μg i.p. for 14 days | Xenograft volume↓ Free radical scavenging Incidence↓ Number of tumors per mouse↓ | [198] | |
| DMBA-initiated and TPA-promoted papillomas in female ICR mice | 85 nmol/L for 21 days; topical application | Prevent onset of skin tumor | [199] | |
| DMBA/TPA model in CD-1 mice | 1, 5, 10, 25 μmol Twice/week, for 18 Wk; topical application | Skin tumor incidence↓ Apoptosis↑; p53↑; Bax↑; cytochrome C↑; APAF↑; Bcl2↓ | [200] | |
| DMBA-TPA–model in male Swiss albino mice | 50 μmol/mouse for 3–24 week; topical application | Inhibits photocarcinogenesis; Cox2↓; lipid peroxidation↓; ODC↓ | [201] | |
| UVB-mediated photocarcinogenesis in female SKH-1 mice | 25 μmol/mouse; topical application | Decrease hyperplasia; p53↑; Cox2↓; ODC↓; survivin↓ mRNA and protein | [202] | |
| UVB-induced skin hyperplasia in female SKH-1 mice | 10 μmol/mouse; 7 times, on alternate days; topical application | Skin tumor incidence↓ ↑Survivin mRNA and protein; ↑ phospho-survivin; ↓Smac/DIABLO | [203,204]. | |
| UVB-induced skin tumorigenesis in female SKH-1 mice | 25, 50 μmol/mouse; twice/week for 28 weeks; topical application | Suppresses melanoma tumor growth | [205] | |
| C57Bl/6N mice transplanted with B16-BL6 melanoma cells | 50 mg/kg b.w.; i.p. for 19 days | [206] | ||
| Breast | Spontaneous mammary tumor in female FVB/N HER-2/neu mice | 4 μg/mouse/day in drinking water for 2 months | Onset of tumorigenesis↓ Tumor volume↓ Multiplicity↓ Apoptosis↑ | [207] |
| Female athymic mice xenograft models of MDA-MB-231 cells | 25 mg/kg/day i.p. daily for 3 weeks | Tumor volume↓ TUNEL staining↓ Microvessel density↓ | [208] | |
| Female Balb/c mice xenograft with cigarette smoke condensate-transformed, MCF-10A-Tr cells in mammary fat pad | 40 mg/kg/day orally for 30 days | Tumor volume↓ | [209] | |
| DMBA-induced mammary carcinogenesis in female Sprague-Dawley rats | 10 ppm mixed in diet; for 127 days | Suppressed tumor growth NF-κB↓;Cox2↓; MMP9↓ | [210] | |
| DMBA-induced mammary carcinogenesis in female Sprague-Dawley rats | 100 mg/kg b.w. mixed in diet; for 25 weeks | Suppressed tumor growth Cell proliferation↓ Apoptosis↑ | [211] | |
| MNU-induced mammary tumorigenesis in female Sprague-Dawley rats | 100 mg/kg b.w. by oral gavage for 127 days | Estrogen modulation Reduces tumor growth | [212] | |
| MDA-MB-231 breast tumor xenograft model | 25 mg/kg b.w, by i.p., for 3 weeks | Inhibits tumor growth Apoptosis↑ Angiogenesis↓ | [208] | |
| Female HER-2/neu transgenic mice model | 0.2 mg/kg b.w in drinking water for 2 months | Delays the development and reduces the metastatic growth of spontaneous mammary tumors Apoptosis↑ ↓HER-2/neu mRNA and protein | [207] | |
| MDA-MB-231 breast tumor xenograft model in female athymic nu/nu mice | 5 and 25 mg/kg b.w., thrice a week by oral gavage for 117 days, | In combination with quercetin and catechin retards the growth of tumor | [213] | |
| Prostate | Athymic nude mice xenograft models of PC-3 cells | 30 mg/kg/day Thrice/week, total 6 weeks | Tumor volume↓ Cell proliferation↓ Apoptosis↑ Number of blood vessels↓ | [214] |
| Male nude mice xenograft models with Du145-EV-Luc or Du145-MTA1 shRNA-Luc in anterior prostate | 50 mg/kg/day i.p. daily 14 days after implantation, total 6 weeks | Tumor growth↓ Progression, local invasion↓ Spontaneous metastasis↓ Angiogenesis↓ Apoptosis↑ | [215] | |
| Transgenic adenocarcinoma of mouse prostate (TRAMP) model | 625 mg/kg mixed in diet for 7–23 weeks | ER-β ↑; IGF-I ↑; ↓phospho-ERK-1;↓ERK-2 | [216] | |
| Transgenic rat adenocarcinoma of prostate (TRAP) model | 50, 100 or 200 μg/ml in drinking water for 7 weeks | Apoptosis ↑; ↓AR; ↓GK11 mRNA | [217] | |
| Lung | Female C57BL/6 mice xenograft models of LLC tumors | 0.6, 2.5 or 10 mg/kg/day i.p. daily for 21 days | Tumor volume/weight↓ Metastasis to lung↓ | [218] |
| Nude mice xenograft models of A549 | 15, 30 or 60 mg/kg i.v. daily for 15 days | Tumor volume↓ | [219] | |
| C57BL/6 mice implanted with Lewis lung carcinoma lung tumor model | 5 and 25 mg/kg, i.p. for 15 days | Metastasis↓ Angiogenesis↓ | [220] | |
| C57BL/6 mice implanted with Lewis lung carcinoma lung tumor model | 20 mg/kg, i.p. for 17 days | Angiogenesis↓ Apoptosis ↑ | [221] | |
| Colon | DMH models in male Wistar rats | 8 mg/kg/day orally daily for 30 weeks | Incidence↓, Tumor volume↓, Tumor burden/rat↓ Histopathological lesions DMH↓ | [222] |
| BP models in male ApcMin mice | 45 μg/kg/day orally, for 60 days | Number of colon adenomas↓ Dysplasia occurrence↓ | [223] | |
| AOM induced colon cancer in male F344 rats | 200 μg/kg b.w. in drinking water | Bax↑; p21↑ | [224] | |
| ApcMin/+ mice model | 0.01% in drinking water for 7 weeks | Reduce formation of tumor in small intestine cyclin D1 and D2↓ | [225] | |
| ApcMin/+ mice model | 240 mg/kg b.w. mixed in diet for 10–14 weeks | Suppress intestinal adenoma formation Cox1 and 2↓; PGE2↓ | [226] | |
| Liver | Male Donryu rats xenograft models of AH109A cells | 10, 50 ppm in diet for 20 days | Tumor weight↓ Metastasis↓ | [227] |
| Male Wistar rats implanted with AH- 130 hepatoma cells | 1 mg/kg; 7 days; i.p. | Tumor weight↓ Apoptosis↑ ↑cells at G2/M | [228] | |
| BALB/c mice implanted with H22 hepatoma cells | 500, 1000, 1500 mg/kg; 10 days; abdominal injection | Immunomodulatory activity↑ | [229] | |
| BALB/c mice implanted with H22 hepatoma cells | 5, 10, 15 mg/kg; 10 days; abdominal injection | Tumor volume↓ Apoptosis↑ cyclin B1↓; p34cdc2↓ | [230] | |
| BALB/c mice implanted with H22 hepatoma cells | 5, 10, 15 mg/kg; 10 days; abdominal injection | Synergistic anti-tumor effect in combination with 5-FU; S-phase arrest | [231] | |
| Female BALB/c mice implanted with HepG2 cells | 15 mg/kg; every alternate day for 21 days; i.p. | Tumor growth↓ Apoptosis↑ Caspase 3↑ | [232] | |
| DENA-initiated GST-P-positive hepatic pre-neoplastic foci in male Sprague–Dawley rats | 15% (w/w) grape extract in diet; 11 weeks | Tumor growth↓ Lipid peroxidation↓ Fas ↓ | [233] | |
| DENA-initiated and PB-promoted hepatocyte nodule formation in female Sprague–Dawley rats | 50, 100, 300 mg/kg; 20 weeks; diet | Tumor growth↓ Apoptosis↑ Cell proliferation↓ Bcl2↓; Bax↑ | [234] |
↓: downregulated; ↑: upregulated; UVB: ultraviolet B; DMBA: 7,12-Dimethylbenz[a]anthracene; MNU: methyl-N-nitrosourea; AOM: azoxymethane; DENA: diethylnitrosamine; GST-P: glutathione S-transferase; PB: phenobarbital ; p53: tumor protein p53; Bax: Bcl-2-associated-X-protein; APAF: Apoptotic protease activating factor 1; Bcl2: B-cell lymphoma 2; Cox: cyclooxygenase; ODC: ornithine decarboxylase; Smac/DIABLO: Second mitochondriaderived activator of caspases /Diablo homolog; TUNEL: Terminal deoxynucleotidyl transferase dUTP nick end labeling; NF-κB: nuclear factor kappa-light-chain-enhancer of activated B cells; MMP9: matrix metalloproteinase nine; HER-2: human epidermal growth factor receptor 2; ER-β: estrogen receptor beta; IGF-I: insulin-like growth factor 1ERK: extracellular regulated kinase; AR: androgen receptor; GK11: glandular kallikrein 11; DMH: 1,2-dimethylhydrazine ; PGE2: prostaglandin E2; 5-FU: 5-fluorouracil.