The molecular shape and the field similarities as criteria to interpret SAR studies for fragment-based design of platinum(IV) anticancer agents. Correlation of physicochemical properties with cytotoxicity

Molecular shape similarity and field similarity have been used to interpret, in a qualitative way, the structure-activity relationships in a selected series of platinum(IV) complexes with anticancer activity. MM and QM calculations have been used to estimate the electron density, electrostatic potential maps, partial charges, dipolar moments and other parameters to correlate the stereo-electronic properties with the differential biological activity of complexes. Extended Electron Distribution (XED) field similarity has been also evaluated for the free 1,4-diamino carrier ligands, in a fragment-based drug design approach, comparing Connolly solvent excluded surface, hydrophobicity field surface, Van der Waals field surface, nucleophilicity field surface, electrophilicity field surface and the extended electron-distribution maxima field points. A consistency has been found when comparing the stereo-electronic properties of the studied series of platinum(IV) complexes and/or the free ligands evaluated and their in vitro anticancer activity.     

Red notoginseng: higher ginsenoside content and stronger anticancer potential than Asian and American ginseng

A systematic comparison of the ginsenosides and anticancer activities was performed among white (air-dried) and red (steamed) roots of notoginseng (NG, Panax notoginseng), Asian ginseng (AG, P. ginseng), and American ginseng (AmG, P. quinquefolius). Chemical profiles of different ginseng species were characterized, through simultaneous quantification of nineteen major ginsenosides, by HPLC-UV at 202 nm. The antiproliferative and pro-apoptotic effects on human colorectal cancer cells were determined by MTS method and flow cytometry, respectively. Chemical analysis indicated that white NG possessed the most abundant ginsenosides, i.e., two- and five-fold higher than white AmG and AG. During the steaming process, extensive conversion of the original polar ginsenosides in white ginseng to new, less polar, degradation compounds in red ginseng was observed. White ginsengs produced weak antiproliferative effects, while red ginsengs exhibited a significant increase in antiproliferative and pro-apoptotic effects (both P < 0.01 vs. white ginseng). Among the three red ginsengs, red NG showed the best anticancer activity. Due to the low cost of NG and high bioactivity of red NG, the red NG is promising to be a useful botanical product in cancer chemoprevention.     

In vitro antioxidative and anticancer activities of tea glycoprotein in green tea

In this paper, the antioxidative and anticancer activities of tea glycoprotein (TGP) in green tea were studied. TGP was extracted from coarse old green tea and purified by Sephadex G-100 gel filtration, and its purity was determined by high performance gel permeation chromatography (HPGPC). The antioxidative activity of the TGP was evaluated by determining the change of the values of the heat-induced oxidation in a linoleic acid system with β-carotene, the decoloration of the 1,1-diphenyl-2-picrylhydrazyl (DPPH), and the superoxide generated from autoxidation of pyrogallol. The results show that the TGP possesses distinctive antioxidative activity. Furthermore, the anticancer activity of the TGP at different concentrations was evaluated by the MTT assay using two kinds of colon cancer cell lines (HCT-15, Caco-2). Dose-dependently TGP exhibited good antiproliferation activity to HCT-15, whereas exhibited very weak antiproliferation activity to Caco-2. Only at a very high concentration (409.6 μmol L⁻¹), the TGP obviously inhibited the proliferation of Caco-2. Whether there is a correlation between the antioxidative and the anticancer activity of the TGP, should be studied further.     

Potential use of antioxidative mungbean protein hydrolysate as an anticancer asiatic acid carrier

This study investigated the potential use of mungbean (Vigna radiata (L.) Wilczek) protein hydrolysate (MPH) prepared from tryptic hydrolysis as an antioxidative hydrolysate and as a carrier for anticancer asiatic acid (AA). The antioxidant capacity of MPH was 0.67 and 0.46 ??mol Trolox equivalent (TE)/mg protein, as measured by oxygen radical absorbance capacity-fluorescein (ORAC_FL) and Trolox equivalent antioxidant capacity (TEAC) assays, respectively. Freeze-drying in lactose excipient reduced the antioxidant capacity of MPH to 0.48 ??mol TE/mg protein in ORAC_FL assay (P < 0.05) but did not alter antioxidant capacity determined by TEAC assay (P ≥ 0.05). The genotoxicity of H₂O₂ (50 ??M, 30 min) on hepatoblastoma HepG2 could be alleviated after HepG2 cells had taken up MPH after H₂O₂ exposure (P < 0.05). Moreover, the inhibition concentration (IC₅₀) of AA in HepG2 was lowered from 58.5 ??g mL^− 1 of AA alone to 38.5 ??g mL^− 1 when AA was freeze-dried with MPH in lactose excipient (P < 0.05). This study suggested that the efficacy of anticancer pentacyclic triterpene AA against hepatoblastoma HepG2 could be increased by co-drying with antioxidative mungbean protein hydrolysate in lactose excipient.     

Synthesis,Structural Characterization,and Ability to Inhibit Cancer Growth of a Series of Organotin Poly(ethylene glycols)

A series of organotin poly(ethylene glycols) were synthesized including the first water soluble organotin polymers. These products are all polymeric with weight average molecular weights about 10⁵. Infrared spectroscopy shows the presence of moieties from both reactants and the formation of the Sn–O linkage. F MALDI MS shows the presence of up to over a hundred units and by isotopic abundance the presence of one, two, and three tin-containing ion fragments. The polymers inhibit the growth of cancer cell lines from bone, prostate, colon, breast, and lung cancers. In a number of instances chemotherapeutic index values of two and greater are found consistent with these polymers being more active against cancer cells than non-cancerous healthy cells. Thus, some of these polymers show good promise as a new family of anticancer drugs including the water-soluble organotin-containing polymers.     

Biological Properties of Melanoidins: A Review

Melanoidins are brown, high molecular weight products of Maillard reaction, which takes place during thermal processing of food. They are formed in a multistage reaction between reducing sugars and compounds possessing free amino groups and found in roasted coffee, bakery products, cooked meat, beer, honey, sweet wine, processed tomatoes, and fiber. Nowadays, melanoidins have attracted a lot of attention, not only as a functional food ingredient, but also as a potential pro-healthy dietary supplement. In this field, their antioxidant, antimicrobial, anticancer, and detoxifying activity have been described. Based on recent research developments, an overview of the biological properties of melanoidins with implications for human health is presented.     

纳米材料介导的siRNA和抗癌药物递送系统的研究进展

RNA干扰(RNAi)正逐步成为癌症治疗中强而有力的技术手段。siRNA可被设计用于特异沉默那些参与耐药及化疗无效基因的表达,是一种重要的RNAi的工具。目前,可以通过si RNA和其他组合疗法的协同效应来提高抗肿瘤药物的治疗效果。然而,共同递送这些多样的抗癌药物需要设计相应的纳米载体。将重点介绍基于脂质体、聚合物和无机纳米载药体系的si RNA和抗癌药物共同递送系统,并讨论基于纳米载体递送系统下的si RNA及抗癌药物的联用情况。     

In vitro and in vivo evaluation of anticancer actions of natural and synthetic vitamin E forms

The goal of these studies was to investigate the potential anticancer properties of two naturally occurring plant sources and two manufactured synthetic forms of vitamin E, i. e., RRR-alpha-tocopherol (alphaT), RRR-gamma-tocopherol (gammaT), all-rac-alpha-tocopherol (all-rac-alphaT), and all-rac-alpha-tocopheryl acetate (all-rac-alphaTAc) in breast cancer models. Vitamin E compounds were evaluated in vitro for inhibition of colony formation and induction of apoptosis in human MDA-MB-435 and MCF-7 breast cancer cells and murine 66cl-4 mammary cancer cells and in vivo for ability to reduce tumor growth and lung and lymph node metastases using the transplantable syngeneic BALB/c mouse 66cl-4-GFP mammary cancer model. gammaT inhibited colony formation and induced apoptosis in all three cancer cell lines. alphaT and all-rac-alphaT were less effective and all-rac-alphaTAc was ineffective. gammaT-induced apoptosis was correlated with activation of caspases-8 and -9 and down-regulation of protein expression of c-FLIP and survivin. In vivo study 1 analyses showed that all-rac-alphaT and all-rac-alphaTAc significantly inhibited tumor growth and inhibited both visible and microscopic size lung metastases. In vivo study 2 analyses showed that alphaT and gammaT reduced tumor growth, but only gammaT reduced tumor growth significantly in comparison to control. In conclusion, synthetic, but not natural, vitamin E exhibits promising anti-cancer properties in vivo.