RT Journal Article
A1 van Ginkel, Paul R.
A1 Darjatmoko, Soesiawati R.
A1 Sareen, Dhruv
A1 Subramanian, Lalita
A1 Bhattacharya, Saswati
A1 Lindstrom, Mary J.
A1 Albert, Daniel M.
A1 Polans, Arthur S.
T1 Resveratrol Inhibits Uveal Melanoma Tumor Growth via Early Mitochondrial Dysfunction
JF Investigative Ophthalmology & Visual Science
JO Invest. Ophthalmol. Vis. Sci.
YR 2008
DO 10.1167/iovs.07-1233
VO 49
IS 4
SP 1299
OP 1306
SN 1552-5783
AB   purpose. To test the efficacy of resveratrol, a nontoxic plant product, in the treatment of uveal melanoma.  methods. The effect of oral administration and peritumor injection of resveratrol was tested on tumor growth in two animal models of uveal melanoma. The mechanism of resveratrol action on uveal melanoma cells was studied in vitro in a cell-viability assay: with JC-1 dye, to measure mitochondrial membrane potential; by Western blot analysis, to analyze the cellular redistribution of cytochrome c and Smac/diablo; and in a fluorescence assay with specific substrates, to measure activation of different caspases.  results. Resveratrol treatment inhibited tumor growth in animal models of uveal melanoma. Since oral administration resulted in relatively low bioavailability of resveratrol, the effect of increased local levels was tested by peritumor injection of the drug. This method resulted in tumor cell death and tumor regression. In vitro experiments with multiple uveal melanoma cell lines demonstrate that resveratrol causes a decrease in cell viability, resulting at least in part from an increase in apoptosis through a mitochondrial pathway. An early event in drug action is the direct targeting of mitochondria by resveratrol, which leads to a decrease in mitochondrial membrane potential and the eventual activation of caspase-3. Conclusion These data suggest that resveratrol can inhibit tumor growth and can induce apoptosis via the intrinsic mitochondrial pathway and that by further increasing bioavailability of resveratrol the potency of the drug can be increased, leading to tumor regression. The nontoxic nature of the drug at levels needed for therapy make resveratrol an attractive candidate for the treatment of uveal melanoma. 
RD 4/23/2021
UL https://doi.org/10.1167/iovs.07-1233