Table 1.

In vivo effects of resveratrol on cancer development and growth and their possible mechanisms

Target/effectsMechanismsDose/durationRouteReferences
Skin
    Reduces the number of skin tumors initiated with DMBA and promoted by TPA in female CD-1 mice↓COX-1; ↓COX-2; ↓c-myc; ↓c-fos; ↓c-Jun; ↓TGF-β1; ↓TNF-α1, 5, 10, 25 μmoltop.Jang et al. (12); Jang and Pezzuto (13)
Twice/week for 18 wk
    Suppresses the development of DMBA-initiated and TPA-promoted papillomas in female ICR miceFree radical scavenging85 nmol/Ltop.Kapadia et al. (14)
21 wk
    Reduces the onset of skin tumors with DMBA-TPA model in CD-1 mice1, 5, 10, 25 μmoltop.Soleas et al. (15)
Twice/week, 18 wk
    Inhibits the development of DMBA-TPA–induced skin tumors in male Swiss albino mice↑Apoptosis; ↑Bax; ↑p53; ↓ Bcl-2; ↑cytochrome c release; ↑APAF-150 μmol/mousetop.Kalra et al. (16)
3-24 week
    Prevents UVB-mediated photocarcinogenesis in female SKH-1 mice↓COX; ↓ODC; ↓lipid peroxidation25 μmol/mousetop.Afaq et al. (17)
    Decreases UVB-induced skin hyperplasia in female SKH-1 mice↑CDK-2, CDK-4, and CDK-6; ↑ cyclin D1 and cyclin D2; ↑ MAPK; ↑ p21; ↑p53; ↓COX-2; ↓ODC; ↓survivin mRNA and protein10 μmol/mousetop.Reagan-Shaw et al. (18); Aziz et al. (19)
7 times, alternate days
    Prevents UV radiation-mediated skin tumorigenesis in female SKH-1 mice↑Survivin mRNA and protein; ↑ phospho-survivin; ↓Smac/DIABLO25, 50 μmol/mousetop.Aziz et al. (20)
Twice/week, 28 wk
    Delays tumor growth in female C57Bl/6N mice transplanted with B16-BL6 melanoma cells50 mg/kgi.p.Caltagirone et al. (21)
19 d
    Does not slow down the growth of B16M melanoma cells inoculated into the footpad of male C57Bl/6J mice20 mg/kgp.o.Asensi et al. (22)
23 mg/mLd.w.
10 d
    Does not inhibit the growth of A375 human melanoma cells xenografted in male nu/nu mice0.005, 0.01%d.w.Niles et al. (23)
0.0025, 0.006%Diet
10, 25, 50, 100 mgs.p.
Breast
    Suppresses DMBA-induced mammary carcinogenesis in female Sprague-Dawley rats↓NF-κB; ↓COX-2; ↓MMP-910 ppmDietBanerjee et al. (24)
127 d
    Suppresses DMBA-induced mammary cancer in Sprague-Dawley rats↓Proliferation; ↑apoptosis100 mg/kgDietWhitsett et al. (25)
25 wk
    In combination with genistein improves the tumor inhibitory action of resveratrol in DMBA-initiated rat mammary carcinogenesis100, 333 mg/kgDietWhitsett and Lamartiniere (26)
Lifetime
    Reduces MNU-induced mammary tumorigenesis in female Sprague-Dawley ratsEstrogen modulation100 mg/kgp.o.Bhat et al. (27)
127 d
    Increases MNU-induced mammary carcinogenesis in female Sprague-Dawley ratsEndocrine disruption100 mg/kgs.c.Sato et al. (28)
37 wk
    Inhibits the growth of MDA-MB-231 breast tumor explants in female athymic nude mice↑Apoptosis; ↓angiogenesis25 mg/kgi.p.Garvin et al. (29)
3 wk
    Does not influence the growth and metastasis of transplanted 4T1 mammary carcinoma cells in female BALB/c mice1, 3, 5 mg/kgi.p.Bove et al. (30)
23 d
    Delays the development and reduces the metastatic growth of spontaneous mammary tumors in female HER-2/neu transgenic mice↑Apoptosis; ↓HER-2/neu; mRNA and protein0.2 mg/kgd.w.Provinciali et al. (31)
2 mo
    In combination with quercetin and catechin retards the growth of xenografts of MDA-MB-231 cells in female athymic nu/nu mice5, 25 mg/kgp.o.Schlachterman et al. (32)
Thrice/week, 117 d
Prostate
    Suppresses prostate cancer progression in male TRAMP model↑ER-β; ↑IGF-I; ↓phospho-ERK-1and ERK-2625 mg/kgDietHarper et al. (33)
7-23 wk
    Suppresses prostate cancer growth in male TRAP rats↑Apoptosis; ↓AR; ↓GK11 mRNA50, 100, 200 μg/mLd.w.Seeni et al. (34)
7 wk
Gastrointestinal tract
    Inhibits AOM-induced colon carcinogenesis in male F344 rats↑Bax; ↑p21200 μg/kgd.w.Tessitore et al. (35)
100 d
    Suppresses DMH-induced colon carcinogenesis in male Wistar ratsModulation of antioxidant defense and biotransformation enzymes8 mg/kgp.o.Sengottuvelan et al. (3638)
15-29 wk
    Prevents the formation of colon tumors and reduces small intestinal tumors in ApcMin/+ mice↓Cyclin D1 and cyclin D2; ↓DP1; ↓YB1; ↑TGF-β; ↑TSG101 (all mRNA)0.01%d.w.Schneider et al. (39)
7 wk
    Decreases intestinal adenoma formation in ApcMin/+ mice↓COX-1; ↓COX-2; ↓PGE2240 mg/kgDietSale et al. (40)
10-14 wk
    Does not affect intestinal tumorigenesis in male ApcMin/+ mice4, 20, 90 mg/kgDietZiegler et al. (41)
7 wk
    Inhibits NMBA-induced esophageal tumorigenesis in male F344 rats↓COX-1 and COX-2 mRNA; ↓PGE21, 2 mg/kgp.o. or i.p.Li et al. (42)
16-20 wk
    Inhibits the growth of implanted human primary gastric carcinoma cells in female BALB/c nude mice↑Apoptosis; ↑Bax and ↓Bcl-2 (mRNA and protein)500, 1,000, 1,500 mg/kgi.t.Zhou et al. (43)
6 times in 11 d
    Does not modify BOP-induced pancreatic carcinogenesis in male Syrian hamsters10 ppmDietKuroiwa et al. (44)
3-14 wk
    Decreases the growth of transplanted Yoshida AH-130 ascites hepatoma cells in male Wistar rats↑Cells in G2-M phase; ↑apoptosis1 mg/kgi.p.Carbó et al. (45)
7 d
    Suppresses tumor growth and metastasis in male Donryu rats implanted with AH-109A ascites hepatoma cells↓Serum TG; ↓VLDL; ↓LDL50 ppmDietMiura et al. (46)
20 d
    Inhibits the weight of tumors in BALB/c mice implanted with H22 hepatoma cellsImmunomodulation500, 1,000, 1500 mg/kgabdLiu et al. (47)
10 d
    Reduces the volume of tumors in BALB/c mice implanted with H22 tumors↓Cyclin B1; ↓p34cdc25, 10, 15 mg/kgabdYu et al. (48)
10 d
    Enhances the antitumor effect of 5-fluorouracil in male BALB/c mice implanted with H22 tumorsS phase5, 10, 15 mg/kgabdWu et al. (49)
10 d
    Inhibits DENA-initiated hepatocarcinogenesis in female Sprague-Dawley rats↓Proliferation; ↑apoptosis; ↑Bax; ↓Bcl-250, 100, 300 mg/kgDietBishayee and Dhir (50)
20 wk
Lung
    Does not influence lung tumorigenesis induced by B[a]P and NNK in female A/J mice500 ppmDietHecht et al. (51)
25 wk
    Does not reduce the number or size of B[a]P-induced lung tumors in female A/J mice6-8 mg/kgDietBerge et al. (52)
∼5 mo
    Inhibits tumor growth and lung metastasis in female C57Bl/6 mice transplanted with Lewis lung carcinoma cells↑Apoptosis; ↓DNA synthesis; ↓angiogenesis2.5, 10 mg/kgi.p.Kimura and Okuda (53)
21 d
    Decreases metastasis of implanted Lewis lung carcinoma cells in C57Bl/6 mice↓Angiogenesis5, 25 mg/kgi.p.Busquets et al. (54)
15 d
    Inhibits tumor growth in female C57Bl/6 mice inoculated with Lewis lung carcinoma cells; an analogue is found more potent↑Apoptosis; ↓angiogenesis20 mg/kgi.p.Lee et al. (55)
17 d
Other systems
    Suppresses the growth of implanted neuro-2a neuroblastoma cells in male A/J mice↑Apoptosis; S phase; ↓p21; ↑cyclin E40 mg/kgi.p.Chen et al. (56)
28 d
    Inhibits the growth of implanted RT-2 glioma cells in F344 rats↑Apoptosis; ↓angiogenesis40 or 100 mg/kgi.p.Tseng et al. (57)
4 wk
    Represses tumor growth in Fischer rats inoculated with RT-2 glioma cells↓Angiogenesis; ↓CD3140 mg/kgi.p.Chen et al. (58)
4 wk
    Diminishes the growth of NGP and SK-N-AS neuroblastoma cells in athymic mice↑Apoptosis; mitochondrial dysfunction; ↑cytochrome c release; ↑Smac/DIABLO release; ↑caspases2, 10, 50 mg/kgp.o.van Ginkel et al. (59)
5 wk
    Exhibits weak antileukemic effects in male C3H (H-2k) mice with 32Dp210 cells↑Apoptosis; ↑caspase-380 mg/kgp.o.Gao et al. (60)
5 times/week; 14-60 d
    Enhances antitumor immune activity in male BALB/c mice bearing L1210 lymphocytic leukemic cells↑Apoptosis; ↓Bcl-2; ↓IL-6 mRNA and protein12.5, 25, 50 mg/kgi.g.Li et al. (61)
3 wk
    Inhibits the growth of implanted T241 fibrosarcoma cells in C57Bl6/J mice↓Angiogenesis1 mg/kgd.w.Bråkenhielm et al. (62)
∼23 d
    Retards the growth of inoculated C918 and Mum2b cells in athymic mice↑Apoptosis; mitochondrial dysfunction; ↑cytochrome c release; ↑Smac/DIABLO release; ↑caspase-30.4-50 mg/kgp.o.van Ginkel et al. (63)
3-5 wk

Abbreviations: TGF, transforming growth factor; TNF, tumor necrosis factor; APAF-1, apoptotic protease-activating factor-1; MAPK, mitogen-activated protein kinase; MMP-9, matrix metalloproteinase-9; MNU, N-methyl-N-nitrosourea; IGF-I, insulin-like growth factor-I; TRAMP, transgenic adenocarcinoma mouse prostate; TRAP, transgenic rat for adenocarcinoma of prostate; AR, androgen receptor; GK11, glandular kallikrein 11; AOM, azoxymethane; DMH, 1,2-dimethylhydrazine; NMBA, N-nitrosomethylbenzylamine; BOP, N-nitrosobis(2-oxopropyl)amine; TG, triglyceride; VLDL, very low-density lipoprotein; LDL, low-density lipoprotein; DENA, diethylnitrosamine; NNK, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone; IL-6, interleukin-6; top., topical; p.o., per os; d.w., drinking water; s.p., slow-release pellet; abd, abdominal injection; i.t., intratumoral.