Twenty nine Amaryllidaceae alkaloids and their derivatives belonging to five most common groups, including lycorine-, lycorenine-, tazettine-, crinine-, and narciclasine-types, were evaluated for antiproliferative, apoptosis inducing and antiinvasive activities in vitro. The antiproliferative properties of each test compound are in agreement with those reported in the literature, while the high potency of amarbellisine is reported for the first time. It was also found that with the exception of ungeremine, amarbellisine and hippeastrine, the antiproliferative effect of the potent compounds is apoptosis-mediated. Thus, apoptosis in Jurkat cells was triggered by narciclasine, narciclasine tetraacetate, C10b-R-hydroxypancratistatin, cis-dihydronarciclasine, trans-dihydronarciclasine, lycorine, 1-O-acetyllycorine, lycorine-2-one, pseudolycorine, and haemanthamine. With the exception of narciclasine, lycorine and haemanthamine, the apoptosis inducing properties of these compounds are reported for the first time. The collagen type I invasion assay revealed potent antiinvasive properties associated with N-methyllycorine iodide, hippeastrine, clivimine, buphanamine, and narciclasine tetraacetate, all of which were tested at non-toxic concentrations. The antiinvasive activity of buphanamine is particularly promising since this alkaloid is not toxic to cells even at much higher doses. This work has resulted in identification of several novel leads for anticancer drug design.
A novel microfluidic reactor for in situ small-angle X-ray scattering (SAXS) and X-ray absorption fine structure spectroscopy (XAFS) of Pd colloidal nanoparticles synthesis is reported. The microreactor allows time resolution ranging from milliseconds to several minutes with a residence time of over an hour. The synthesis of colloidal Pd nanoparticles is investigated in the presence of oleylamine and trioctylphosphine ligands. For both ligands, SAXS results show the synthesis proceeds through slow, continuous nucleation as evidenced by a continuous increase in the number of particles. Growth is autocatalytic and fast at the early times; then, despite the availability of a large percentage of unreacted Pd precursor, growth slows dramatically and the Pd nanoparticle diameter reaches a plateau while more nanoparticles continue to form. In situ XAFS reveals an increase in Pd−P coordination coinciding with the time of slowed growth. The combined SAXS and XAFS results strongly suggest that the capping ligands play an important role in slowing growth by binding to the nanoparticle surface leading to a self-limiting nanoparticle size. Despite the slow continuous nucleation and overlapped fast autocatalytic growth, 1 nm Pd nanoparticles with narrow size distribution (±20%) can be synthesized using strong capping ligands (e.g., trioctylphosphine).
Abstract. Ethnotraditional use of plant-derived natural products plays a significant role in the discovery and development of potential medicinal agents. Plants of the genus Taraxacum, commonly known as dandelions, have a history of use in Chinese, Arabian and Native American traditional medicine, to treat a variety of diseases including cancer. To date, however, very few studies have been reported on the anti-carcinogenic activity of Taraxacum officinale (TO). In the present study, three aqueous extracts were prepared from the mature leaves, flowers and roots, and investigated on tumor progression related processes such as proliferation and invasion. Our results show that the crude extract of dandelion leaf (DLE) decreased the growth of MCF-7/AZ breast cancer cells in an ERK-dependent manner, whereas the aqueous extracts of dandelion flower (DFE) and root (DRE) had no effect on the growth of either cell line. Furthermore, DRE was found to block invasion of MCF-7/ AZ breast cancer cells while DLE blocked the invasion of LNCaP prostate cancer cells, into collagen type I. Inhibition of invasion was further evidenced by decreased phosphorylation levels of FAK and src as well as reduced activities of matrix metalloproteinases, MMP-2 and MMP-9. This study provides new scientific data on TO and suggests that TO extracts or individual components present in the extracts may be of value as novel anti-cancer agents. IntroductionPlants of the genus Taraxacum, also known as dandelions, are members of the Asteraceae family. These perennial plants are widespread throughout the warmer temperate zones of the Northern Hemisphere and have been used for centuries as a remedy for various ailments by several societies. Dandelions play a pivotal role in traditional Chinese medicine (TCM) and are frequently used for treatment of breast, uterine and lung tumors as well as hepatitis and digestive diseases (1,2), while Native Americans use dandelion roots and herbs to treat kidney disease, dyspepsia and heartburn. In traditional Arabian medicine, dandelions have been applied to remedy liver and spleen disorders (3), whereas European herbalists authorize the use of dandelions for fever, boils, eye problems, diabetes and diarrhea (4).The variety of health benefits associated with the use of dandelions has been attributed to specific Taraxacum species as extracts of the whole plants or specific plant parts. Anticarcinogenic activities have been reported for the aqueous root extract of Taraxacum japonicum on mouse skin tumors (5). Further study revealed that taraxasterol and taraxerol, triterpenoids isolated from T. japonicum, were responsible for the observed effect on mouse skin tumors and that taraxasterol inhibited spontaneous mammary carcinogenesis, after oral administration (6). Taraxinic acid, isolated from Taraxacum coreanum showed potent antiproliferative activity against HL-60 cells (7) and the ethanolic extracts of the Chinese dandelion root (Taraxacum mongolicum) inhibited the growth of B16 2F2 mouse melanoma cells (8). Antitumor...
The mechanisms of invasion and metastasis are poorly understood. Our previous studies demonstrated that cancer cell invasion may result from reorganization of membrane molecules, thereby initiating signaling pathways. To increase our understanding on how cancer cells govern metastases we studied the established LNCaP prostate cancer progression model. Herein we show that the bone metastatic derivative cell line, C4-2B, displays changes in adhesion to collagen type I and invasion into collagen type I. Moreover, we found that these changes were concomitant with activation of the FAK/src/paxillin/Rac/JNK signaling pathway and increased activity of matrix metalloproteinases (MMPs)-2 and -9. Inhibition of src and JNK resulted in inhibition of adhesion and invasion, and deactivation of the signaling molecules in the identified pathway as well as reduced activity of MMPs. Additionally, we found a pivotal role for the integrin α2 subunit since lateral redistribution and clustering were responsible for activation of the downstream signaling and function blocking of the integrin α2 subunit resulted in poor adhesion and inhibition of invasion. In conclusion, our results suggest that invasion of prostate cancer cells can be ascribed to reorganization and clustering of integrin α2 subunits, resulting in activation of associated FAK/src/paxillin/Rac/JNK, leading to increased activity of MMPs and thus invasion.
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