ABSTRACT
Natural products and their derivatives are important components of anti-tumor drugs. Currently, anti-tumor drugs derived from natural products which are in clinical practice are mainly conventional cytotoxic or molecularly targeted drugs. Their application is limited by drug-related side effects and drug resistance. Recent studies have shown that anti-tumor natural products often act on multiple targets in tumor cells and in turn interfere with multiple processes in tumorigenesis and development. As tumor is a systemic disease induced by multiple factors, multi-targeted natural products possess unique potential in tumor therapy. However, the targets and mechanisms of the discovered multi-targeted antitumor natural products remain elusive, which limits their further development and application. This review summarized the research progress in the mechanism of action, target identification, and structure optimization of multi-targeted anti-tumor natural products exemplified by a few typical compounds. The research and development of these agents have also been proposed.
ABSTRACT
CRISPR/Cas9 system, consisting of clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) proteins, is a prokaryotic immune system that confers resistance to foreign genetic elements such as those present within plasmids and phages. A simple version of the CRISPR/Cas system, type Ⅱ CRISPR, has been modified to edit genomes. By delivering the Cas9 nuclease together with a synthetic guide RNA (sgRNA) into cells, genome can be edited at desired loci site. CRISPR/Cas genome editing techniques have been widely implemented in various species and research areas. In this review, we summarize the several applications of CRISPR/Cas9 in the field of drug discovery and development, which include target gene screening and editing, drug target screening and validation, generation of animal models and treatment of genetic disease, etc. The defects and improvements of CRISPR/Cas9 technology is discussed as well.
ABSTRACT
PURPOSE: Genes involved in liver cancer cell growth have been identified using an antisense library of large circular (LC-) genomic DNA of a recombinant M13 phage. MATERIALS AND METHODS: A subtracted cDNA library was constructed by combining procedures of suppression subtractive hybridization (SSH) and unidirectional cloning of the subtracted cDNA into an M13 phagemid vector. Utilizing the life cycle of M13 bacteriophages, LC-antisense molecules derived from 1, 200 random cDNA clones selected by size were prepared from the culture supernatant of bacterial transformants. The antisense molecules were arrayed for transfection on 96-well plates preseeded with HepG2. RESULTS: When examined for growth inhibition after antisense transfection, 153 out of 1, 200 LC-antisense molecules showed varying degrees of growth inhibitory effect to HepG2 cells. Sequence comparison of the 153 clones identified 58 unique genes. The observations were further extended by other cell-based assays. CONCLUSION: These results suggest that the LC-antisense library offers potential for unique high-throughput screening to find genes involved in a specific biological function, and may prove to be an effective target validation system for gene-based drug discovery.