[Vic]

Anticarcinogenicity Studies of Resveratrol

Test System or Species,

Strain, and Age, Number,

and Sex of Animals

Chemical Form

and Purity

Route, Dose, Duration, and

Observation Period

Results/Comments

Reference

In Vitro Assays
Mammary glands of mice, BALB/c, 3- to 4-wk-old,number n.p., F

resveratrol, purity n.p.

incubation with 1, 2.5, 5, and 10 µM (0.2, 0.57, 1, and 2.3 µg/mL) for the first 10 days of 14-day culture (Ductal lesions were induced with 2 µg/mL DMBA on day 3 for 24 h.)

The incidence of hyperplastic and aggressive ductal lesions
induced by DMBA was reduced by resveratrol in a dose dependent manner (IC50 ~3 µM).

Bhat et al. (2001)

Human breast cancer cell
lines: ER-positive KPL-1
and MCF-7 and ERnegative MKL-F

trans-resveratrol,
99.8% pure

incubation with 0.01-40 µg/mL (0.04-180 µM) for 24, 48, 72, and 96 h At ≥44 µM, the growth of all cell lines was inhibited in time- and
dose-dependent manners.
The IC50 for the 72-h treatment ranged from 105 to 149 µM. At lower concentrations of resveratrol,moderate inhibition of the growth of MKL-F and stimulation of
KPL-1 and MCF-7 in a time-dependent manner were seen. At 72 h, the cells were stimulated by up to 132 and 115% of control level, respectively.

Nakagawa et al. (2001)

Human breast cancer cell
lines: hormone-sensitive
MCF-7 and T47-D and
hormone-resistant MDAMB-
231

(+)-resveratrol,
>99% pure

incubation with 10-12 – 10-6 M
(1 pM-1 µM [2 x 10-7 -0.2 µg/mL]) for a total of 6 days;applied on day 2 (one cell cycle) and day 5 (three cell
cycles)

Cell proliferation was inhibited in a dose-dependent manner in all cell lines; the effect after day 5 was more apparent than at day 2. The IC50 and maximum inhibition of resveratrol were as follows:
IC50 (pM) Inhibition
MCF-7 13.7±8.3 0.42
T47-D 0.1±1.2 0.56
MDA-MB-231 5.2±9.1 0.30

Damianaki et al. (2000)


Prostate cancer cell lines:
hormone-sensitive LNCaP,PC3, and DU145

(+)-resveratrol,
>99% pure

incubation with 10-12 – 10-6 M
(1 pM-1 µM [2 x 10-7 -0.2 µg/mL]) given one day after seeding (day 0) and cultured for 6 days

Resveratrol had no effect in LNCaP cells (IC50 = >10-6 M). At >10-7 M, resveratrol produced partial inhibition of growth in the PC3 cell line (IC50 = 0.11±1.23 x 10-6 M; maximum inhibition at 0.48). In DU145 cells, it was a potent inhibitor of cell growth, which was time- and dose-dependent (IC50 = 0.57±0.58 x 10-12 M; maximum inhibition at 0.82). In LNCaP cells, resveratrol was a very weak competitor of androgen binding.

Kampa et al. (2000)

Prostate cancer cell line
LNCaP

resveratrol, purity
n.p.

incubation with up to 200 µM (45.7 µg/mL) for 24 or 32 h with or without Mib 2 days after cells were seeded

At 100 µM, Mib-stimulated cell growth was inhibited and very little apoptosis was observed. At 200 µM, massive apoptotic cell death was seen.

Mitchell et al.
(1999)

In Vivo Assays
Mice, C57B16/J
(implanted s.c. with a
murine T241 fibrosarcoma
in the middle dorsum
[tumors visible after 72 h]), 5- to 6-wk-old, 6-7M/group

resveratrol, >99% pure

oral; 5.7 µg/mL (25 µM) or 1 mg/kg/day in absolute ethanol added to drinking water for 25 days

Resveratrol significantly inhibited the growth of T241
fibrosarcomas in the animals.

Bråkenhielm et al. (2001)

Rats, F344, 2-mo-old,
10M/group

resveratrol, purity
n.p.

oral; 200 µg/kg (0.876 µmol/kg) bw/day in drinking water for 100 days beginning 10 days before s.c. injection of 2 doses of 15 mg/kg AOM 1 wk apart

The number of ACF in the colorectal mucosa (25.7±3.6 vs.
39.4±3.3 in controls) and mean multiplicity (2.7±0.3 vs. 4.9±0.6 in controls) were significantly reduced. Resveratrol also reduced the number of small and medium ACF and stopped the development of large ACF. Compared to controls, bax was significantly expressed in ACF of
treated rats (53±1.3% and 57±1.3%, respectively) but not in the surrounding mucosa. In addition, p21 was expressed in ACF of treated rats but to a lower degree compared to controls (1.5±0.1% and 2.2±0.1%, respectively) but not in the normal mucosa.

Tessitore et al. (2000)

Rats, Sprague-Dawley, 42-days-old, 20F/group

resveratrol, purity n.p.

intragastric; 10 and 100 mg/kg (0.044 and 0.438 mmol/kg) bw 5 days/wk starting 7 days before NMU administration and terminating 120 days after administration of NMU

By day 21, tumors were palpable in the control group after NMU administration. By day 111, 100% incidence was reached. The high dose of resveratrol delayed tumorigenesis: on day 40, 0% incidence was observed versus 42% incidence in the control group; the median time for appearance of the first tumor was 79.5 days in the treated group versus 51.5 days in the control group; at
termination, the multiplicity of tumors was 3.9 versus 6.0 in
control animals. There was also a decrease in the total number of tumors. Morphologically, there was an increase in differentiated alveolar structures among tumor parenchyma, focal reduction of cell layers and numerous luminal openings within alveolar structures, and necrosis and apoptotic cells in small areas of some tumors.

Bhat et al. (2001)