Targeted Delivery of Resveratrol Prevents Lung Cancer in Model

A team of Swiss cancer researchers prevented development of lung cancer in a mouse model system using a method, which they had developed, that delivered high concentration dosages of the natural cancer chemoprevention compound resveratrol directly to the animals' lungs.

Resveratrol (trans-3,5,4'-trihydroxystilbene), a compound found largely in the skins of red grapes, is a component of Ko-jo-kon, a form of oriental medicine used to treat diseases of the blood vessels, heart, and liver. Red wine contains between 0.2 and 5.8 milligrams per liter of resveratrol, depending on the grape variety, while white wine has much less - the reason being that red wine is fermented with the skins, allowing the wine to absorb the resveratrol, whereas white wine is fermented after the skin has been removed. Resveratrol came to scientific attention during the mid-1990s as a possible explanation for the "French Paradox" - the low incidence of heart disease among the French, who eat a relatively high-fat diet. Since then, it has been promoted by manufacturers and examined by scientific researchers as an antioxidant, an anti-cancer agent, and a phytoestrogen.

Resveratrol's low oral bioavailability has often limited the translation of promising in vitro activities to beneficial in vivo effects. For example, while oral administration of resveratrol effectively inhibited colorectal carcinogenesis, it failed to protect mice from chemically induced lung cancer.

To increase the amount of the compound reaching the lungs, investigators at the University of Geneva (Switzerland) devised a method for the intranasal administration of a concentrated resveratrol solution. This formulation was administered three times a week for 25 weeks to A/J mice having 4-[methyl(nitroso)amino]-1-(3-pyridinyl)-1-butanone-induced lung carcinogenesis.

The investigators reported in the September 24, 2018, online edition of the journal Scientific Reports that the resveratrol concentration obtained in the lungs after nasal administration of the formulation was 22 times higher than when taken orally. Resveratrol-treated mice showed a 27% decrease in tumor multiplicity, with smaller tumors, resulting in 45% decrease in tumor volume/mouse. When comparing two groups that were exposed to a carcinogen, 63% of the resveratrol treated mice did not develop cancer, compared to only 12.5% of untreated mice.

"We tried to prevent lung cancer induced by a carcinogen found in cigarette smoke by using resveratrol, an already well-documented molecule, in a mouse model," said senior author Dr. Muriel Cuendet, associate professor of pharmaceutical sciences at the University of Geneva. "We observed a 45% decrease in tumor load per mouse in the treated mice. They developed fewer tumors and of smaller size than untreated mice. Resveratrol could therefore play a preventive role against lung cancer."

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