Understanding the Antiproliferative Activity of Plant Extracts

Many plants possess medicinal properties. Some, such as the Pacific yew, have yielded chemotherapeutic drugs (taxanes). Scientists report that other extracts such as the leaves of Calendula officinalis (marigold), Vinca rosea (periwinkle), Viscum cruciatum (mistletoe), and Rosmarinus officinalis (rosemary) have anti-tumor activity. In most cases, the chemical components responsible for antiproliferative activity have not been identified and it is unclear if any individual components are as effective in isolation as they are in the context of the whole extract. Furthermore, in most cases, there are no data indicating whether these extracts have synergistic effects or cause negative reactions when used with other drugs. We are using HeLa (adenocarcinoma), RAW 264.7 (leukemia), HepG2 (hepatoma), MDA-MB-231 (adenocarcinoma), and human foreskin fibroblasts (HFF, non-tumorigenic) to test the antiproliferative activity of several plant extracts. We identified five extracts, grapeseed, guava, yew, juniper berry, and Vinca, that slow the growth of all five cell lines in a dose-dependent manner. We are using a variety of methods to understand the mechanism by which these extracts are blocking cell growth

Melanocortin receptor accessory proteins in adrenal disease and obesity.

Melanocortin receptor accessory proteins (MRAPs) are regulators of the melanocortin receptor family. MRAP is an essential accessory factor for the functional expression of the MC2R/ACTH receptor. The importance of MRAP in adrenal gland physiology is demonstrated by the clinical condition familial glucocorticoid deficiency type 2. The role of its paralog melanocortin-2-receptor accessory protein 2 (MRAP2), which is predominantly expressed in the hypothalamus including the paraventricular nucleus, has recently been linked to mammalian obesity. Whole body deletion and targeted brain specific deletion of the Mrap2 gene result in severe obesity in mice. Interestingly, Mrap2 complete knockout (KO) mice have increased body weight without detectable changes to food intake or energy expenditure. Rare heterozygous variants of MRAP2 have been found in humans with severe, early-onset obesity. In vitro data have shown that Mrap2 interaction with the melanocortin-4-receptor (Mc4r) affects receptor signaling. However, the mechanism by which Mrap2 regulates body weight in vivo is not fully understood and differences between the phenotypes of Mrap2 and Mc4r KO mice may point toward Mc4r independent mechanisms