The Role of Resveratrol in Cancer Therapy
Abstract
:1. Introduction
2. In Vitro Pharmacological Properties and Anti-Cancer Effects of Resveratrol
3. Anti-Tumor-Initiation Activity
4. Anti-Tumor-Promotion Activity
5. Anti-Tumor-Progression Activity
6. Pre-Clinical Studies
7. Skin Cancer
8. Breast Cancer
9. Prostate Cancer
10. Colorectal Cancer
11. Liver Cancer
12. Pancreatic Cancer
13. Lung Cancer
14. Other Cancers
15. Clinical Trials with Resveratrol
16. Conclusions and Future Perspectives
Acknowledgments
Author Contributions
Conflicts of Interest
References
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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] |
Participants | Resveratrol Formulation and Dosages | Outcome | References |
---|---|---|---|
Colorectal cancer patients (n = 8) | Grape powder (80 or 120 g/day) or Resveratrol (20 or 80 mg/day) for 2 weeks | Inhibition of Wnt target gene expression in normal colonic mucosa. | [320] |
Colorectal cancer patients (n = 20) | Resveratrol (0.5 or 1g) for 8 days | Reduction of Ki-67 levels by 5 and 7% in cancerous and normal tissue, respectively. | [322] |
Colorectal cancer patients with hepatic metastasis (n = 6) | Micronized resveratrol (SRT5001, 5 g) for 14 days | Detection of resveratrol in hepatic tissue and increased (39%) content of cleaved caspase-3 in malignant hepatic tissue. | [315] |
Multiple myeloma patients (n = 24) | Micronized resveratrol (SRT5001, 5 g) for 20 days in a 21 day cycle up to 12 cycles | Unacceptable safety profile and minimal efficacy in patients with relapsed/refractory multiple myeloma highlighting the risks of novel drug development in such populations. | [316] |
Biochemically recurrent prostate cancer patients (n = 14) | Pulverized muscadine grape skin extract (MPX) 4000 mg/patient | MPX was found to be safe and warrants further investigation in dose-evaluating phase II trial | [323] |
Benign prostate hyperplasis patients (n = 66) | Two doses of resveratrol (150 mg or 1000 mg resveratrol daily) for 4 months | Significantly lowered the serum levels of androgens with no changes in prostate tumor growth. | [324] |
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Ko, J.-H.; Sethi, G.; Um, J.-Y.; Shanmugam, M.K.; Arfuso, F.; Kumar, A.P.; Bishayee, A.; Ahn, K.S. The Role of Resveratrol in Cancer Therapy. Int. J. Mol. Sci. 2017, 18, 2589. https://doi.org/10.3390/ijms18122589
Ko J-H, Sethi G, Um J-Y, Shanmugam MK, Arfuso F, Kumar AP, Bishayee A, Ahn KS. The Role of Resveratrol in Cancer Therapy. International Journal of Molecular Sciences. 2017; 18(12):2589. https://doi.org/10.3390/ijms18122589
Chicago/Turabian StyleKo, Jeong-Hyeon, Gautam Sethi, Jae-Young Um, Muthu K Shanmugam, Frank Arfuso, Alan Prem Kumar, Anupam Bishayee, and Kwang Seok Ahn. 2017. "The Role of Resveratrol in Cancer Therapy" International Journal of Molecular Sciences 18, no. 12: 2589. https://doi.org/10.3390/ijms18122589
APA StyleKo, J. -H., Sethi, G., Um, J. -Y., Shanmugam, M. K., Arfuso, F., Kumar, A. P., Bishayee, A., & Ahn, K. S. (2017). The Role of Resveratrol in Cancer Therapy. International Journal of Molecular Sciences, 18(12), 2589. https://doi.org/10.3390/ijms18122589