Nontoxic Glucomoringin-Isothiocyanate (GMG-ITC) Rich Soluble Extract Induces Apoptosis and Inhibits Proliferation of Human Prostate Adenocarcinoma Cells (PC-3).

The incidence of prostate cancer malignancy along with other cancer types is increasing worldwide, resulting in high mortality rate due to lack of effective medications. Moringa oleifera has been used for the treatment of communicable and non-communicable ailments across tropical countries, yet, little has been documented regarding its effect on prostate cancer. We evaluated the acute toxicity and apoptosis inducing effect of glucomoringin-isothiocyanate rich soluble extracts (GMG-ITC-RSE) from M. oleifera in vivo and in vitro, respectively. Glucomoringin was isolated, identified, and characterized using fundamental analytical chemistry tools where Sprague-Dawley (SD) rats, murine fibroblast (3T3), and human prostate adenocarcinoma cells (PC-3) were used for acute toxicity and bioassays experiments. GMG-ITC-RSE did not instigate adverse toxic reactions to the animals even at high doses (2000 mg/kg body weight) and affected none of the vital organs in the rats. The extract exhibited high levels of safety in 3T3 cells, where more than 90% of the cells appeared viable when treated with the extract in a time-dependent manner even at high dose (250 µg/mL). GMG-ITC-RSE significantly triggered morphological aberrations distinctive to apoptosis observed under microscope. These findings obviously revealed the putative safety of GMG-ITC-RSE in vivo and in vitro, in addition to its anti-proliferative effect on PC-3 cells.

Mechanism-specific and whole-organism ecotoxicity of mono-rhamnolipids.

Biosurfactants like rhamnolipids are promising alternatives to chemical surfactants in a range of applications. A wider use requires an analysis of their environmental fate and their ecotoxicological potential. In the present study mono-rhamnolipids produced by a recombinant Pseudomonas putida strain were analyzed using the Green Toxicology concept for acute and mechanism-specific toxicity in an ecotoxicological test battery. Acute toxicity tests with the invertebrate Daphnia magna and with zebrafish embryos (Danio rerio) were performed. In addition, microbial and fungicidal effectiveness was investigated. Mutagenicity of the sample was tested by means of the Ames fluctuation assay. A selected mono-rhamnolipid was used for model simulations regarding mutagenicity and estrogenic activity. Our results indicate that mono-rhamnolipids cause acute toxicity to daphnids and zebrafish embryos comparable to or even lower than chemical surfactants. Rhamnolipids showed very low toxicity to the germination of Aspergillus niger spores and the growth of Candida albicans. No frameshift mutation or base substitutions were observed using the Ames fluctuation assay with the two tester strains TA98 and TA100. This result was confirmed by model simulations. Likewise it was computed that rhamnolipids have no estrogenic potential. In conclusion, mono-rhamnolipids are an environmental friendly alternative to chemical surfactants as the ecotoxicological potential is low.

Rhamnose-coated superparamagnetic iron-oxide nanoparticles: an evaluation of their in vitro cytotoxicity, genotoxicity and carcinogenicity.

Tumor recurrence after the incomplete removal of a tumor mass inside brain tissue is the main reason that scientists are working to identify new strategies in brain oncologic therapy. In particular, in the treatment of the most malignant astrocytic tumor glioblastoma, the use of magnetic nanoparticles seems to be one of the most promising keys in overcoming this problem, namely by means of magnetic fluid hyperthermia (MFH) treatment. However, the major unknown issue related to the use of nanoparticles is their toxicological behavior when they are in contact with biological tissues. In the present study, we investigated the interaction of glioblastoma and other tumor cell lines with superparamagnetic iron-oxide nanoparticles covalently coated with a rhamnose derivative, using proper cytotoxic assays. In the present study, we focused our attention on different strategies of toxicity evaluation comparing different cytotoxicological approaches in order to identify the biological damages induced by the nanoparticles. The data show an intensive internalization process of rhamnose-coated iron oxide nanoparticles by the cells, suggesting that rhamnose moiety is a promising biocompatible coating in favoring cells' uptake. With regards to cytotoxicity, a 35% cell death at a maximum concentration, mainly as a result of mitochondrial damages, was found. This cytotoxic behavior, along with the high uptake ability, could facilitate the use of these rhamnose-coated iron-oxide nanoparticles for future MFH therapeutic treatments.

Enhancement of paclitaxel transport and cytotoxicity by 7,3',4'-trimethoxyflavone, a P-glycoprotein inhibitor.

PURPOSE: Paclitaxel has problems with respect to bioavailability and resistance. The aim of this study was to select a P-glycoprotein (Pgp)- inhibitory flavonoid to enhance paclitaxel bioavailability in the Caco-2 cell monolayer. METHODS: Cytotoxicity and chemosensitization were determined using MTT assay. Paclitaxel transport was examined in the Caco-2 cell monolayer, which mimics the intestinal barrier. Paclitaxel concentrations were quantitated by HPLC assay using the internal standard method. RESULTS: Chemosensitizing indeces of 7,3',4'-trimethoxyflavone (TMF) and verapamil was > 333 and 152, respectively. The basolateral (BL)- to-apical (AP) transport of paclitaxel was more than 10-fold greater than its AP-to-BL transport. TMF and verapamil increased the AP-to-BL transport of paclitaxel but decreased its BL-to-AP transport in a concentration-dependent manner. The net absorptive effect of 50 microM TMF on paclitaxel transport was comparable to that of 50 muM verapamil. In addition, AP loading of TMF increased the paclitaxel sensitivity of paclitaxel-resistant SK-MES-1/PT4000 cells overexpressing Pgp on the BL side. CONCLUSIONS: These results indicate that TMF with low toxicity can be used as an enhancer of oral paclitaxel bioavailability and as a Pgp inhibitor.

The rhamnose moiety of solamargine plays a crucial role in triggering cell death by apoptosis.

Solamargine, solasodine and khasianine steroidal alkaloids are utilized to determine the role of carbohydrate moiety in the mechanism of apoptosis. The C3 side chain of solamargine, khasianine and solasodine contains 4'Rha-Glc-Rha2', 4'Rha-Glc and H, respectively. Solamargine possessed potent cytotoxicity to human hepatoma cells, while the cytotoxicity of khasianine was greatly diminished. Nevertheless, only solamargine could induced "sub-G1" of apoptotic feature in flowcytometry. Thus, the 2'Rha moiety of solamargine may play a crucial role in triggering cell death by apoptosis. In addition, the molecular modeling of solamargine indicated that the 2'Rha moiety was adjacent to the rigid steroid structure, and drastically changed the dihedral angle of the glycosidic bond. The regulations of TNFR I and II expression by different carbohydrate moieties were also distinct. It implied that the carbohydrate moieties of steroidal alkaloids might alter the binding specificity to steroid receptors and consequently regulate the gene expression in different manners.