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Background: RNA-cleaving deoxyribozymes (DNAzymes) are catalytic deoxyribonucleic acid molecules that have become a promising new class of gene suppressors by binding and cleaving target mRNA. This study investigated whether DNAzymes targeting Bcl-xL enhanced the effectiveness of radiotherapy and chemotherapy in colorectal cancer (CRC) cells.
Methods: Two types of CRC cells, SW480 and SW837, were transfected with five DNAzymes. Cell viability, Bcl-xL expression and apoptosis were examined. SW480 xenograft model was used to examine the combined effects of Bcl-xL DNAzymes and 5-FU (or X-rays) on tumor growth.
Results: Three Bcl-xL DNAzymes, DT882, DT883, and DT884 were identified to be effective in suppressing Bcl-xL expression and causing cell apoptosis. Furthermore, DT882 combined with 5-FU or radiotherapy addictively promoted cell apoptosis and significantly inhibited the growth of SW480 xenografts in vivo.
Conclusions: These results suggest that Bcl-xL DNAzymes can enhance the radiosensitivity and chemosensitivity in CRC cells via inducing apoptosis.
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http://dx.doi.org/10.1186/s40360-022-00553-x | DOI Listing |
BMC Pharmacol Toxicol
February 2022
Department of Gastrointestinal Surgery, The 3rd Affiliated Teaching Hospital of Xinjiang Medical University (Affiliated Cancer Hospital), Urumqi, 830010, P. R. China.
Background: RNA-cleaving deoxyribozymes (DNAzymes) are catalytic deoxyribonucleic acid molecules that have become a promising new class of gene suppressors by binding and cleaving target mRNA. This study investigated whether DNAzymes targeting Bcl-xL enhanced the effectiveness of radiotherapy and chemotherapy in colorectal cancer (CRC) cells.
Methods: Two types of CRC cells, SW480 and SW837, were transfected with five DNAzymes.
Autophagy
June 2022
State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
Owing to the dominant functions of mitochondria in multiple cellular metabolisms and distinct types of regulated cell death, maintaining a functional mitochondrial network is fundamental for the cellular homeostasis and body fitness in response to physiological adaptations and stressed conditions. The process of mitophagy, in which the dysfunctional or superfluous mitochondria are selectively engulfed by autophagosome and subsequently degraded in lysosome, has been well formulated as one of the major mechanisms for mitochondrial quality control. To date, the PINK1-PRKN-dependent and receptors (including proteins and lipids)-dependent pathways have been characterized to determine the mitophagy in mammalian cells.
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June 2021
Department of Biotechnology, Faculty of Biomedical Sciences and Technology, SRI RAMACHANDRA Institute of Higher Education and Research (SRIHER), Deemed to be University (DU), Porur, Chennai, Tamil Nadu, 600 116, India.
Matrix metalloproteinases (MMPs) are pivotal for cancer cell migration and metastasis which are generally over-expressed in such cell types. Many drugs targeting MMPs do so by binding to the conserved catalytic domains and thus exhibit poor selectivity due to domain-similarities with other proteases. We report herein the binding of a novel compound [3-(E-3,4-dihydroxycinnamaoyloxyl)-2-hydroxypropyl 9Z, 12Z-octadeca-9, 12-dienoate; Mol.
View Article and Find Full Text PDFCell
February 2021
Genetic Perturbation Platform, Broad Institute, Cambridge, MA 02142, USA. Electronic address:
Understanding the functional consequences of single-nucleotide variants is critical to uncovering the genetic underpinnings of diseases, but technologies to characterize variants are limiting. Here, we leverage CRISPR-Cas9 cytosine base editors in pooled screens to scalably assay variants at endogenous loci in mammalian cells. We benchmark the performance of base editors in positive and negative selection screens, identifying known loss-of-function mutations in BRCA1 and BRCA2 with high precision.
View Article and Find Full Text PDFEXCLI J
September 2020
Faculty of Life Science and Biotechnology, South Asian University, Akbar Bhawan, Chanakyapuri, New Delhi-110021, India.
Breast cancer is the most common cancer among women worldwide. Among different types of breast cancer known, treatment of triple-negative breast cancer is a major challenge because of its aggressiveness and poor prognosis; thus, identification of specific drivers is required for targeted therapies of breast cancer malignancy. Protein Casein Kinase (CSNK) is a serine/threonine kinase that exists as a tetrameric complex consisting of two catalytic (α and /or α') and two regulatory β subunits.
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