Can the Christmas berry primrose plant compound fight uveal melanoma? Researchers at the Sidney Kimmel Cancer Center (SKCC) at Jefferson Health and the Icahn School of Medicine at Mt. Sinai found that a compound extracted from the plant stops the cancer’s growth in preliminary tests. With further testing, the discovery could lead to new therapeutic options for patients with uveal melanoma. “I’m very optimistic,” says Jeffrey Benovic, Ph.D., Thomas Eakins Endowed Professor of Biochemistry and Molecular Biology at Thomas Jefferson University and an Associate Director with the SKCC. “If the results are confirmed in animal models and eventually humans, it could offer a new way to treat metastatic uveal melanoma patients down the road.”
The researchers tested whether a compound derived from an ornamental plant in the primrose family known as Ardisia crenata might be able to fight the disease. The findings were published in the journal Molecular Cancer Research. The compound - FR900359 or simply FR - was discovered 30 years ago from the plant’s leaves. FR works by blocking a particular type of G protein that sits on a cell’s membrane, called Gq, an important signaling molecule. A subset of these proteins are mutated in uveal melanoma, turning on a molecular pathway that leads to cancer growth. “I’m hopeful FR and related compounds will reset the cancer cells in the mouse model as it did in the cells we grew in the lab getting it one step closer to testing in humans,” Benovic added.
The team grew three different types of uveal melanoma cells that have the cancer-spurring mutations in the lab and treated the cells with FR. “We didn’t expect it would work because previous research suggested a related compound called YM-254890 did not inhibit the mutated forms of the proteins found in uveal melanoma,” says graduate student Dominic Lapadula. “But lo and behold, FR very effectively blocked the growth of the uveal melanoma cells. When the uveal melanoma cells were treated with small amounts of FR, the cells appeared to revert from cancer cells to typical melanocytes. FR appears to be able to help reset the cells back to their normal state. Ideally that’s what you want.”
Higher doses of FR killed the cells, and the results suggest the compound could be an effective drug to treat uveal melanoma one day. Doctors diagnose about 2,000 adults with uveal melanoma - a cancer of the eye - every year. Although the condition differs from melanoma of the skin, both cancers are lethal. Uveal melanoma accounts for about five percent of all melanoma cases. Surgery or radiation is the go-to treatment for patients with primary UM that has not spread to other parts of the body, but metastases occur in about half of cases.
Meadowfoam Protects Skin From The Sun
Meadowfoam - a native Pacific Northwest plant cultivated as an oilseed crop and named for the white flowers it produces when a crop is in full bloom - has emerged as a potential new source of protection against the sun's harmful effects on the skin.
Meadowfoam contains a class of compounds known as glucosinolates whose derivatives have been shown to have anti-cancer and sunlight-protectant properties and has emerged as a potential new source of protection against the sun's harmful effects on the skin. The findings by scientists at Oregon State University looked at two derivatives from one such glucosinolate that's found readily in the "seedmeal" left over from meadowfoam oilseed processing.
Prolonged exposure to the sun can lead to the skin's premature aging, visible in the form of sagging and wrinkles. Nearly 10,000 people a day in the United States are diagnosed with skin cancer, resulting in large part from the DNA damage caused by the ultraviolet radiation the sun emits. "There's a highly complex cascade of biochemical reactions that occur as stress responses in the skin attempt to counteract UV-induced damage," says co-corresponding author Gitali Indra, associate professor of pharmaceutical sciences. "We need better ways to block UV exposure and also ways to lessen the damage by limiting detrimental physiological processes."
Skin Cell Damage
The scientists set up 3-D facsimiles of human skin reconstructed in culture plates, hit them with ultraviolet B radiation and then treated the skin with the meadowfoam derivatives. Both of the derivatives - 3- methoxybenzylisothiocyanate and 3-methoxyphenylacetonitrile -ameliorated the UV damage to the skin cells by prohibiting crosslinking of DNA, thereby preventing cancer-initiating mutations; inhibiting two enzymes involved in the breakdown of collagen, skin's primary structural protein; causing a reduction in the number of precancerous cells; and preventing hyperplasia - organ or tissue enlargement that's often an early stage in cancer development. "DNA damage is the precursor to photocarcinogenesis, and these derivatives reduce that damage, which means improved skin health and reduced cancer risk," added Arup Indra, associate professor of pharmaceutical sciences, affiliate investigator at OSU's Linus Pauling Institute and the other co-corresponding author. "The findings show a tremendous potential for utility in skin care products, besides just demonstrating the science on its own."
3D Skin Reconstrucution
The 3D skin reconstructions used in the study represent an important research tool. "It's very important to not use animal models in the testing of cosmetics and skin care products," Indra continued. "People don't like to see animal testing data, especially in Europe, where they'll put a picture of a bunny rabbit on a product so people know animals weren't used in the testing. This is a very good model that we can use to test many kinds of drugs by using different assays. We can look at how a compound slowly diffuses and see how it impacts collagen degradation and UV protection. It's really nice that we can tease apart these different functions."
Because the glucosinolate derivatives inhibit the enzymes needed for the breakdown of collagen, they're effectively acting as anti-aging compounds. "Most cosmetics just sort of patch things up, cover up the damage, but this actually protects the skin," added co-author Fred Stevens, principal investigator at the Linus Pauling Institute and professor of medicinal chemistry in the College of Pharmacy.
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With over 30 years of writing and editing experience for newspapers, magazines and corporate communications, Kevin Kerfoot writes about natural health, nutrition, skincare and oral hygiene for Trusted Health Products’ natural health blog and newsletters.
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