Table 1.

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

    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.
    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)
    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
    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
    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.