A grape constituent protects against cancer

Date: October 3, 2018 Source: Université de Genève Summary: Lung cancer is the deadliest form of cancer in the world, and 80% of death are related to smoking. In addition to tobacco control, effective chemoprevention strategies are therefore needed. A team of scientists studied a well-known natural product, resveratrol, which is found in grapes and in red wine. While its chemopreventive properties against cancers affecting the digestive tract have been documented by previous studies, resveratrol has so far shown no effect on lung cancers. Thanks to nasal administration, the UNIGE team obtained very promising results in a study conducted in mice.

Lung cancer is the deadliest form of cancer in the world, and 80% of death are related to smoking. In addition to tobacco control, effective chemoprevention strategies are therefore needed. A team of scientists from the University of Geneva (UNIGE), Switzerland, studied a well-known natural product, resveratrol, which is found in grapes and in red wine. While its chemopreventive properties against cancers affecting the digestive tract have been documented by previous studies, resveratrol has so far shown no effect on lung cancers. Thanks to nasal administration, the UNIGE team obtained very promising results in a study conducted in mice and described in the journal Scientific Reports.

"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," explains Muriel Cuendet, Associate Professor in the School of pharmaceutical sciences of the UNIGE Faculty of Science. This 26 week long study contained four groups of mice. The first one, the control, received neither carcinogen nor resveratrol treatment. The second received only the carcinogen, the third received both the carcinogen and the treatment, and the fourth received only the treatment. "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," says Muriel Cuendet. When comparing the two groups that were not exposed to carcinogen, 63% of the mice treated did not develop cancer, compared to only 12.5% of the untreated mice. "Resveratrol could therefore play a preventive role against lung cancer," she continues.

This formulation is applicable to humans

However, resveratrol does not seem suitable for preventing lung cancer: when ingested, it is metabolized and eliminated within minutes, and therefore does not have time to reach the lungs. "This is why our challenge was to find a formulation in which resveratrol could be solubilized in large quantities, even though it is poorly soluble in water, in order to allow nasal administration. This formulation, applicable to humans, allows the compound to reach the lungs," explains Aymeric Monteillier, a scientist in the School of pharmaceutical sciences of the UNIGE Faculty of Science, and the first author of the study. The resveratrol concentration obtained in the lungs after nasal administration of the formulation was 22 times higher than when taken orally. The chemoprevention mechanism is probably related to apoptosis, a process by which cells program their own death and from which cancer cells escape. The UNIGE research team will now focus on finding a biomarker that could contribute to the selection of people eligible for preventive treatment with resveratrol.

Towards a preventive treatment?

Resveratrol is an already well-known molecule, which is found in food supplements, meaning that no further toxicological study would be needed prior to commercialisation as a preventive treatment. "This discovery is unfortunately of little economic interest to pharmaceutical groups. The molecule is indeed simple and non-patentable and cancer prevention studies require a follow-up over many years," regrets Muriel Cuendet, without excluding the development of preventive treatment in humans.

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Journal Reference:

Aymeric Monteillier, Aymone Voisin, Pascal Furrer, Eric Allémann, Muriel Cuendet. Intranasal administration of resveratrol successfully prevents lung cancer in A/J mice. Scientific Reports, 2018; 8 (1) DOI: 10.1038/s41598-018-32423-0

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Université de Genève. "A grape constituent protects against cancer." ScienceDaily. ScienceDaily, 3 October 2018. <www.sciencedaily.com/releases/2018/10/181003102423.htm>.

Newly discovered compounds shed fresh light on whole grain health benefits

Date: October 3, 2018 Source: University of Eastern Finland Summary: Scientists have discovered new compounds that may explain whole grain health benefits. A high intake of whole grains increased the levels of betaine compounds in the body which, in turn, was associated with improved glucose metabolism, among other things. The findings shed new light on the cell level effects of a whole grain-rich diet, and can help in development of increasingly healthy food products.

Scientists have discovered new compounds that may explain whole grain health benefits, reports a new study led by the University of Eastern Finland. A high intake of whole grains increased the levels of betaine compounds in the body which, in turn, was associated with improved glucose metabolism, among other things. The findings shed new light on the cell level effects of a whole grain-rich diet, and can help in the development of increasingly healthy food products.

"Whole grains are one of the healthiest foods there is. For instance, we know that a high intake of whole grains protects against type 2 diabetes and cardiovascular diseases. Up until now, however, we haven't understood the cellular mechanisms through which a whole grain-rich diet impacts our body," says Dr Kati Hanhineva, Principal Investigator of the study at the University of Eastern Finland.

Using metabolomics analysis, Dr Hanhineva's research group investigated the effects of a whole grain-rich diet on the body's metabolites. The effects were studied in mice fed with bran-rich fodder, and in humans following a diet rich in whole grain products over the course of 12 weeks. A whole grain-rich diet increased the levels of betaine compounds in both mice and humans.

"This is the first time many of these betaine compounds were observed in the human body in the first place," Dr Hanhineva says.

At the end of the 12-week follow-up, the researchers also observed a correlation between improved glucose metabolism and increased presence of betaine compounds in the body.

"Pipecolic acid betaine, for example, is particularly interesting. Increased levels of pipecolic acid betaine after the consumption of whole grains was, among other things, associated with lower post-meal glucose levels."

New compound worked similarly to a heart drug in cell level experiments

One of the betaine compounds discovered by the researchers is 5-aminovaleric acid betaine, 5-AVAB, which seems to cumulate in metabolically active tissues, such as the heart. With this observation in mind, the researchers set out to further test its effects in a cell model.

"We observed that 5-AVAB reduces cardiomyocytes' use of fatty acids as a source of energy by inhibiting the function of a certain cell membrane protein," Researcher Olli Kärkkäinen from the University of Eastern Finland says.

"This cell level effect is similar to that of certain drugs used for cardiovascular diseases. However, it is important to keep in mind that we haven't proceeded beyond cell level experiments yet. We need further research in animals and humans to verify that 5-AVAB really can impact the function of our body."

However, the discovery of the new compounds associated with whole grains significantly enhances our understanding of why whole grain products are good for our health.

"In the future, we seek to analyse in greater detail the multitude of effects these new compounds can have on the human body, and we will also look into how intestinal microbes possibly contribute to the formation of these compounds," Dr Hanhineva continues.

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Materials provided by University of Eastern Finland. Note: Content may be edited for style and length.

Journal Reference:

Olli Kärkkäinen, Maria A Lankinen, Marilena Vitale, Jenna Jokkala, Jukka Leppänen, Ville Koistinen, Marko Lehtonen, Rosalba Giacco, Natalia Rosa-Sibakov, Valérie Micard, Angela A A Rivellese, Ursula Schwab, Hannu Mykkänen, Matti Uusitupa, Marjukka Kolehmainen, Gabriele Riccardi, Kaisa Poutanen, Seppo Auriola, Kati Hanhineva. Diets rich in whole grains increase betainized compounds associated with glucose metabolism. The American Journal of Clinical Nutrition, 2018; DOI: 10.1093/ajcn/nqy169

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University of Eastern Finland. "Newly discovered compounds shed fresh light on whole grain health benefits." ScienceDaily. ScienceDaily, 3 October 2018. <www.sciencedaily.com/releases/2018/10/181003102720.htm>.