Grafting of a novel gold(III) complex on nanoporous MCM-41 and evaluation of its toxicity in Saccharomyces cerevisiae

The goal of this research was to investigate the potential of newly synthesized gold complex trichloro(2,4,6-trimethylpyridine)Au(III) as an anticancer agent. The gold(III) complex was synthesized and grafted on nanoporous silica, MCM-41, to produce AuCl3@PF-MCM- 41 (AuCl3 grafted on pyridine-functionalized MCM-41). The toxicity of trichloro(2,4,6- trimethylpyridine)Au(III) and AuCl3@PF-MCM-41 in Saccharomyces cerevisiae (as a model system) was studied. The gold(III) complex showed a mid cytotoxic effect on yeast viability. Using the drug delivery system, nanoporous MCM-41, the gold(III) complex became a strong inhibitor for growth of yeast cells at a very low concentration. Furthermore, the animal tests revealed a high uptake of AuCl3@PF-MCM-41 in tumor cells. The stability of the compound was confirmed in human serum

Preparing Nanoarchaeosome Containing Triptorelin Acetate and Evaluation of Its Cellular Toxic Effect on PC3 Prostate Cancer Cell Line

Background and objectives: Prostate cancer is the second leading cause of mortality among men worldwide, and the eighth cancer-related cause of death in Iran. Male sex hormones (androgens) are the main cause of prostate cancer cells. Triptorelin is considered a synthetic decapeptide analogue of gonadotropin-releasing hormone (GnRH) in the treatment of prostate cancer. This study aimed to evaluate the methods to deal with the constraints in use of lipid nanoarchaeosomes. Due to their adjuvant feature and presence of ether links, archaeosomes are more stable in blood, compared to other lipid-based formulations. In the present study, the effects of nanoarchaeosomes containing triptorelin acetate on the cellular toxicity of the PC3 prostate cancer cell line were evaluated. Methods: Halobacterium salinarum bacteria were cultured in HS medium, and their polar lipids of the membrane were removed applying the Blight&Dye technique in order to obtain nanoarchaeosome containing membrane polar lipids. In the next stage, nanoarchaeosomes were prepared by the hydration of polar lipids. In addition, cell viability was evaluated using the MTT assay on the PC3 cell line. Results: In this research, mean diameter of the drug-containing nanoarchaeosomes was estimated at 263 nm using the ZetaSizer device. Moreover, drug loading efficiency of nanoarchaeosomes was estimated at 98%. Furthermore, the toxicity of the free and nanoarchaeosome drugs was assessed via the MTT assay, results of which were indicative of a mean of IC 50 0.22 µg/ml in this regard. Conclusion: According to the results of the study, archaeosomes extracted from polar lipids were produced with high concentration and purity on the nanoscale. Considering the high stability, ease of production, level of drug loading, and toxic effect on cancer cells, nanoarchaeosomes can be used as a suitable technique for targeted drug delivery in future studies

Prospects and challenges of cancer systems medicine: from genes to disease networks

It is becoming evident that holistic perspectives toward cancer are crucial in deciphering the overwhelming complexity of tumors. Single-layer analysis of genome-wide data has greatly contributed to our understanding of cellular systems and their perturbations. However, fundamental gaps in our knowledge persist and hamper the design of effective interventions. It is becoming more apparent than ever, that cancer should not only be viewed as a disease of the genome but as a disease of the cellular system. Integrative multilayer approaches are emerging as vigorous assets in our endeavors to achieve systemic views on cancer biology. Herein, we provide a comprehensive review of the approaches, methods and technologies that can serve to achieve systemic perspectives of cancer. We start with genome-wide single-layer approaches of omics analyses of cellular systems and move on to multilayer integrative approaches in which in-depth descriptions of proteogenomics and network-based data analysis are provided. Proteogenomics is a remarkable example of how the integration of multiple levels of information can reduce our blind spots and increase the accuracy and reliability of our interpretations and network-based data analysis is a major approach for data interpretation and a robust scaffold for data integration and modeling. Overall, this review aims to increase cross-field awareness of the approaches and challenges regarding the omics-based study of cancer and to facilitate the necessary shift toward holistic approaches

Ubiquitin and fusarium resistance: Lessons from wheat cDNAS conferring deoxynivalenol resistance in yeast

The production of the trichothecene mycotoxin deoxynivalenol (DON) is an important virulence factor of the plant pathogenic fungus Fusarium graminearum on wheat. We have engineered a DON sensitive yeast strain and constructed a cDNA library from DON treated wheat suspension culture cells in a yeast expression vector. The library was used to select DON resistance conferring clones. Besides ORFs of unknown function, we found 3 classes of cDNAs that in addition to DON resistance conferred hypersensitivity to hygromycin and canavanine. The predicted functions of several of the wheat cDNAs (putative E3 ligase, ubiquitin specific protease, proteasome subunit) suggested a role for ubiquitin-proteasome mediated protein degradation in DON resistance. Results with a coupled wheat germ in vitro translation system and a GUS-luciferase fusion gene showed that DON is a powerful translation elongation inhibitor. The truncated proteins formed in the presence of DON most likely lead to ubiquitin depletion and consequently growth inhibition in yeast. Ubiquitin is essential for many processes in plants, including plant defense. Our results warrant the re-evaluation of the relevance of proteasome system components found to be differentially regulated during Fusarium infection