Gold complexes as prospective metal-based anticancer drugs

Medical and therapeutic value of gold has been recognized thousands of years ago, but its rational use in medicine has not begun until the early 1920s. Cisplatin is one of the first metal-containing compounds with anti-cancer activity discovered in the 1960s. Despite the fact that cisplatin treatment is efficient for several types of solid tumors, its effectiveness is limited by toxic side effects and tumor resistance that often leads to the occurrence of secondary malignancies. Since gold(III) is isoelectronic with platinum(II) and tetracoordinate gold(III) complexes have the same square-planar geometries as cisplatin, the anticancer activity of gold(III) compounds has been investigated. Previous studies suggested that, in contrast to cisplatin, gold complexes target proteins but not DNA. Recently, we have investigated gold(III) dithiocarbamates for their anticancer activity and showed that their primary target is the proteasome. Treatment of human breast tumorbearing nude mice with a gold(III) dithiocarbamate complex resulted in significant inhibition of tumor growth, associated with proteasome inhibition and massive apoptosis induction in vivo. Better understanding of physiological processing of gold compounds will provide a rational basis for their further development into novel anticancer drugs

Impact of the poly(propylene oxide)-b-poly(dimethylsiloxane)-b-poly(propylene oxide) macrodiols on the surface related properties of polyurethane copolymers

Segmented thermoplastic polyurethane copolymers (PURs) were synthesized using 4,4'-methylenediphenyl diisocyanate and 1,4-butanediol as the hard segment and alpha,omega-dihydroxy-poly(propylene oxide)-b-poly(dimethylsiloxane)-b-poly(propylene oxide) (PPO-PDMS) as the soft segment. The content of incorporated soft segments in PURs varied in the range from 40 to 90 wt.%. The structure, molecular weights and crystallinity of obtained copolymers were monitored by FTIR, H-1- and 2D-NMR spectroscopy, and GPC and DSC analysis, respectively. Surface free energy analysis indicates the presence of hydrophobic (siloxane) groups on the surface, giving highly hydrophobic nature to the obtained PURs films. Water absorption measurements showed that the increase of the hydrophobic PPO-PDMS segment content led to the decrease of percentage of absorbed water in copolymers. SEM and AFM analysis revealed that copolymers with lower content of PPO-PDMS segments have higher microphase separation between segments. The results obtained in this work indicate that synthesized PURs based on PPO-PDMS demonstrated proper surface and morphological properties with a great potential for variety of applications such as hydrophobic coatings in biomedicine

Tea polyphenols, their biological effects and potential molecular targets

Tea is the most popular beverage in the world, second only to water. Tea contains an infusion of the leaves from the Camellia sinensis plant rich in polyphenolic compounds known as catechins, the most abundant of which is (-)-EGCG. Although tea has been consumed for centuries, it has only recently been studied extensively as a health-promoting beverage that may act to prevent a number of chronic diseases and cancers. The results of several investigations indicate that green tea consumption may be of modest benefit in reducing the plasma concentration of cholesterol and preventing atherosclerosis. Additionally, the cancer-preventive effects of green tea are widely supported by results from epidemiological, cell culture, animal and clinical studies. In vitro cell culture studies show that tea polyphenols potently induce apoptotic cell death and cell cycle arrest in tumor cells but not in their normal cell counterparts. Green tea polyphenols were shown to affect several biological pathways, including growth factor-mediated pathway, the mitogen-activated protein (MAP) kinasedependent pathway, and ubiquitin/proteasome degradation pathways. Various animal studies have revealed that treatment with green tea inhibits tumor incidence and multiplicity in different organ sites such as skin, lung, liver, stomach, mammary gland and colon. Recently, phase I and II clinical trials have been conducted to explore the anticancer effects of green tea in humans. A major challenge of cancer prevention is to integrate new molecular findings into clinical practice. Therefore, identification of more molecular targets and biomarkers for tea polyphenols is essential for improving the design of green tea trials and will greatly assist in a better understanding of the mechanisms underlying its anti-cancer activity