Phytosterols as anticancer compounds

Phytochemicals have been proposed to offer protection against a variety of chronic ailments including cardiovascular diseases, obesity, diabetes, and cancer. As for cancer protection, it has been estimated that diets rich in phytochemicals can significantly reduce cancer risk by as much as 20%. Phytosterols are specific phytochemicals that resemble cholesterol in structure but are found exclusively in plants. Phytosterols are absorbed from the diet in small but significant amounts. Epidemiological data suggest that the phytosterol content of the diet is associated with a reduction in common cancers including cancers of the colon, breast, and prostate. The means by which dietary phytosterols may be achieving these effects is becoming clearer from molecular studies with tumorigenic research models. Phytosterols affect host systems potentially enabling more robust antitumor responses, including the boosting of immune recognition of cancer, influencing hormonal dependent growth of endocrine tumors, and altering sterol biosynthesis. In addition, phytosterols have effects that directly inhibit tumor growth, including the slowing of cell cycle progression, the induction of apoptosis, and the inhibition of tumor metastasis. This review summarizes the current state of knowledge regarding the anticancer effects of phytosterols.     

Chemotherapeutic engineering: Vitamin E TPGS-emulsified nanoparticles of biodegradable polymers realized sustainable paclitaxel chemotherapy for 168 h in vivo

A full spectrum of proof-of-concept research from nanoparticle preparation and characterization, in vitro drug release, cellular uptake and cytotoxicity, to in vivo pharmacokinetics and xenograft tumor model is developed in this paper to demonstrate how nanoparticles of biodegradable polymers can be applied to formulate anticancer drugs to avoid use of toxic adjuvant and to enable sustained and controlled chemotherapy. Paclitaxel-loaded poly(lactic-co-glycolic acid) nanoparticles were prepared by solvent extraction/evaporation with vitamin E TPGS as the emulsifier, which has much higher emulsification effects and better biocompatibility than other chemical emulsifiers such as polyvinyl alcohol (PVA), resulting in a high drug encapsulation efficiency, high uptake of nanoparticles by cancer cells, and sustainable pharmacokinetics. In vitro C6 cell mortality experiments demonstrated that the nanoparticle formulation was five times more effective than Taxol^®. In vivo pharmacokinetics measurements showed that the nanoparticle formulation had a comparable value of the area-under-the-curve (AUC) with that of Taxol^®, but never exceeded the maximum tolerance level, and hence should greatly reduce the side effects compared with Taxol^®. Moreover, the nanoparticle formulation realized a sustainable therapeutic time of 168 h in comparison with 22 h for Taxol^® at a same dose of 10 mg/kg and achieved four times greater drug tolerance than Taxol^®.     

Synthesis,Structural Characterization,and Initial Evaluation as Anticancer Drugs of Dibutyltin Polyamines Derived from Various 4,6-Diaminopyrimidines

A number of diaminopyrimidines have been incorporated into dibutyltin polyamines with molecular weights ranging from 3.5 × 10⁴ to 3.7 × 10⁶ and product yields from 47 to 88%. Infrared spectroscopy is consistent with the inclusion of the diaminopyridines into the polymer backbone with the IR spectroscopy showing the formation of the Sn–N bond as well as the presence of bands from both reactants being present in the polymer. F MALDI MS is also consistent with the products being polymeric and containing units from both the dibutyltin and pyrimidine reactants. The products exhibit good inhibition of cancer cell lines including those derived from human lung, bone, breast, prostrate, and colon cancers. Inhibition occurs within the same concentration range, and lower than that of the most widely employed chemotherapeutic drug, cisplatin.     

Labdane diterpenes in Curcuma mangga rhizomes inhibit lipid peroxidation,cyclooxygenase enzymes and human tumour cell proliferation

The rhizome of “Mango Ginger”, Curcuma mangga (Zingiberaceae), is a dietary ingredient in India and its popularity is similar to the rhizomes of Curcuma longa (Zingiberaceae), the “turmeric root”. In Indian folk medicine, the rhizomes of C. mangga have been used as medicine to treat a variety of diseases for centuries. However, it has not been investigated for its bioactive constituents. In our study, the aqueous, methanolic and ethyl acetate extracts of its rhizome showed antioxidant, anti-inflammatory and anti-tumour activities. Purification of these active extracts yielded bioactive labdane diterpenoids labda-8(17)-12-diene-15,16-dial (1), calcaratarin A (2), communic acid (3), copallic acid (4), zerumin B (5), 14,15,16-trinor-labdan-8,12-diol (6) and two decalins (7–8). The structures were elucidated by spectral analyses. All pure isolates inhibited lipid peroxidation (LPO) by 12–45% at 25 μg/ml. In cyclooxygenase enzymes (COX-1 and -2) inhibitory assays, compounds 1–4 showed selective COX-2 enzyme inhibition by 39–55% where as 5–8 showed selectivity to COX-1 between 45% and 53%. The tumour cell proliferation inhibition by these compounds was determined by using NCI-H460 (lung), HCT-116 (colon), AGS (gastric), SF-268 (CNS) and MCF-7 (breast) human tumour cell lines. All isolates tested at 25 μg/ml showed some degree of inhibition against tumour cell progression.     

灵芝多糖免疫调节及抗肿瘤作用综述

目的：进一步探讨灵芝多糖免疫调节作用机理。方法：对近年来国内外对灵芝多糖在免疫调节及抗肿瘤方面的研究进展进行综述。结果：灵芝多糖促进免疫细胞数量增长活性增强的药理作用已为众多研究实验所证实。结论：灵芝多糖免疫调节及抗肿瘤作用机理尚未十分明确，但ILEs免疫调节学说的研究为进一步了解多糖免疫作用提供了一个新的研究方向。     

Molecular characteristics of partially hydrolyzed fucoidans from sporophyll of Undaria Pinnatifida and their in vitro anticancer activity

The effects of molecular characteristics on the anticancer activity of fucoidans were investigated after hydrolysis by copper acetate and then fractionation with 30 and 5 kDa membranes, which produced three fucoidan fractions: F_>30 K, F_5–30 K and F_<5 K. The F_>30 K and F_5–30 K consisted of mostly carbohydrate (58.2–61.3%) and sulphate (31.7–35.5%) with small amounts of proteins (1.2–6.4%). However, the major constituents of F_<5 K were sulphate (31.8%) and ash (37.5%) with smaller amounts of carbohydrate (15.5%) and protein (1.2%). The molecular weights (M_w) of F_>30 K, F_5–30 K and F_<5 K, obtained by a light scattering technique, were 262, 5.6 and 1.6 kDa, respectively. The observed anticancer activities were 18.0–28.5% for F_>30 K, 19.2–57.5% for F_5–30 K and 26.5–36.5% for F_<5 K, respectively, in the concentration range of 0.2–0.8 mg/mL. The results suggest that the anticancer activity of fucoidans could be considerably improved by lowering their M_w and by improving the binding properties of sulphate groups possibly through changing the molecular conformation.     

Inhibitory effect of anthraquinones isolated from the Noni (Morinda citrifolia) root on animal A-, B- and Y-families of DNA polymerases and human cancer cell proliferation

During the course of our studies to develop new uses for the Noni (Morinda citrifolia) root, 10 anthraquinones, rubiadin (1), rubiadin 1-methyl ether (2), lucidin (3), damnacanthol (4), 1,3-dihydroxy-2-methoxymethylanthraquinone (5), 3-hydroxy-1-methoxy-2-methoxymethylanthraquinone (6), nordamnacanthal (7), damnacanthal (8), sorandidiol (9) and morindone (10), were isolated. Compounds 5, 6, 7, 8 and 10 exhibited remarkable inhibition against the activities of animal pols, and compound 10 was the strongest inhibitor in the anthraquinones investigated. Among mammalian pols, compound 10 inhibited the pol activities of A- (pol γ), B- (pols α, δ and ε) and Y- (pols η, ι and κ) families, but did not influence the activities of X-family pols (pols β, λ and terminal deoxynucleotidyl transferase). The tendency of pol inhibition showed a positive correlation with the suppression of human colon cancer cell HCT116 growth. These results suggested that the Noni root containing anthraquinones may be used as an anticancer functional food.     

The chemopreventive and anticancer potential against colorectal cancer of polyphenol-rich fruit extracts

The consumption of vegetables and fruits, particularly apples, pomegranates, grapes, and berries, is associated with a decreased risk of developing cancer, especially colorectal cancer (CRC). This may be attributable to the presence of phytochemical constituents, such as polyphenols. This review summarizes the current state of knowledge concerning the chemopreventive and anti-CRC potential of polyphenol-rich apple, pomegranate, grape, and berry extracts with a focus on in vitro, in vivo, and clinical evidence. The extracts demonstrate antiproliferative, proapoptotic, antiangiogenic, antiinvasive, and antimetastatic activities toward colon cancer cell lines and in animal models and markedly influence preneoplastic lesions and malignancies in humans.     

Phytoextract-mediated synthesis of Cu doped NiO nanoparticle using cullon tomentosum plant extract with efficient antibacterial and anticancer property

In the present study, nickel oxide (NiO) and copper-doped nickel oxide (NiCuO) nanoparticles (NPs) were successfully synthesized using Cullen tomentosum plant extract with the co-precipitation method. This work focuses on the Phyto-mediated synthesis and characterization of NPs for their biological applications. Phytochemicals that exist in the plant extract acts as reducing and capping agent. The successful formation of the NPs was validated by various analysis as XRD, FESEM, EDAX, FT-IR, UV–Vis, and Photoluminescence. According to XRD studies, the average crystallite size of NiO and NiCuO NPs is 36 nm and 31 nm, respectively. The river stone and nanoflower like morphology for NiO and NiCuO NPs are confirmed by FESEM image. Furthermore, the synthesized NPs were tested against Gram-positive (Bacillus subtilis, Streptococcus pneumoniae) and Gram-negative (Klebsiella pneumoniae, Escherichia coli) bacteria, which showed enhanced antibacterial activity of NiCuO NPs. The cytotoxicity of NPs was investigated against human breast cancer cells (MDA-MB-231) and fibroblast L929 cell lines. Also, the IC₅₀ value for human breast cancer cells is 11.8 μg/mL. According to these findings, NiCuO NPs are potential nanomaterials with advanced healthcare uses.