Search Results (2)

Osteoporosis is a systemic skeletal disorder affecting over 200 million people worldwide and contributes dramatically to global healthcare costs. Available anti-osteoporotic drug treatments including hormone replacement therapy, anabolic agents, and bisphosphonates often cause adverse events which limit their long-term use. Therefore, the application of natural products has been proposed as an alternative therapy strategy. Icaritin (ICT) is not only an enzyme-hydrolyzed product of icariin but also an intestinal metabolite of eight major flavonoids of the traditional Chinese medicinal plant Epimedium with extensive pharmacological activities, such as strengthening the kidney and reinforcing the bone. ICT displays several therapeutic effects, including osteoporosis prevention, neuroprotection, antitumor, cardiovascular protection, anti-inflammation, and immune-protective effect. ICT inhibits bone resorption activity of osteoclasts and stimulates osteogenic differentiation and maturation of bone marrow stromal progenitor cells and osteoblasts. As for the mechanisms of effect, ICT regulates relative activities of two transcription factors Runx2 and PPARγ, determines the differentiation of MSCs into osteoblasts, increases mRNA expression of OPG, and inhibits mRNA expression of RANKL. Poor water solubility, high lipophilicity, and unfavorable pharmacokinetic properties of ICT restrict its anti-osteoporotic effects, and novel drug delivery systems are explored to overcome intrinsic limitations of ICT. The paper focuses on osteogenic effects and mechanisms, pharmacokinetics and delivery systems of ICT, and highlights bone-targeting strategies to concentrate ICT on the ideal specific site of bone. ICT is a promising potential novel therapeutic agent for osteoporosis. Full article

Malignant melanoma is one of the most metastatic cancer types, and despite recent success with novel treatment strategies, there is still a group of patients who do not respond to any therapies. Earlier, the prenylation inhibitor hydrophilic bisphosphonate zoledronic acid (ZA) was found to inhibit melanoma growth in vitro, but only a weaker effect was observed in vivo due to its hydrophilic properties. Recently, lipophilic bisphosphonates (such as BPH1222) were developed. Accordingly, for the first time, we compared the effect of BPH1222 to ZA in eight melanoma lines using viability, cell-cycle, clonogenic and spheroid assays, videomicroscopy, immunoblot, and xenograft experiments. Based on 2D and spheroid assays, the majority of cell lines were more sensitive to BPH. The activation of Akt and S6 proteins, but not Erk, was inhibited by BPH. Additionally, BPH had a stronger apoptotic effect than ZA, and the changes of Rheb showed a correlation with apoptosis. In vitro, only M24met cells were more sensitive to ZA than to BPH; however, in vivo growth of M24met was inhibited more strongly by BPH. Here, we present that lipophilic BPH is more effective on melanoma cells than ZA and identify the PI3K pathway, particularly Rheb as an important mediator of growth inhibition. Full article