Poly adenosine diphosphate-ribosylation, a promising target for colorectal cancer treatment

The development of colorectal cancer(CRC)can result from changes in a variety of cellular systems within the tumor microenvironment.Particularly,it is primarily associated with genomic instability that is the gradual accumulation of genetic and epigenetic changes consisting of a characteristic set of mutations crucial for pathways in CRC progression.Based on this background,the potential to focus on poly[adenosine diphosphate(ADP)-ribose]polymerase(PARP)-1 and poly-ADP ribosylation(PARylation)as the main causes of malignant formation of CRC may be considered.One of the important functions of PARP-1 and PARylation is its deoxyribonucleic acid(DNA)repair function,which plays a pivotal role in the DNA damage response and prevention of DNA damage maintaining the redox homeostasis involved in the regulation of oxidation and superoxide.PARP-1 and PARylation can also alter epigenetic markers and chromatin structure involved in transcriptional regulation for the oncogenes or tumor suppressor genes by remodeling histone and chromatin enzymes.Given the high importance of these processes in CRC,it can be considered that PARP-1 and PARylation are at the forefront of the pathological changes required for CRC progression.Therefore,this review addresses the current molecular biological features for understanding the multifactorial function of PARP-1 and PARylation in CRC related to the aforementioned roles;furthermore,it presents a summary of recent approaches with PARP-1 inhibition in non-clinical and clinical studies targeting CRC.This understanding could help embrace the importance of targeting PARP-1 and PARylation in the treatment of CRC,which may present the potential to identify various research topics that can be challenged both nonclinically and clinically.

Effect of minocycline on cerebral ischemia-reperfusion injury

Minocylcine, a tetracycline derivate, has been shown to cross the blood-brain barrier and enter the central nervous system. In this study, cerebral ischemia-reperfusion injury models were established using the suture method, and minocycline was immediately injected intraperitoneally after cerebral ischemia-repeffusion （22.5 mg/kg, initially 45 mg/kg） at a 12-hour interval. Results showed that after minocycline treatment, the volume of cerebral infarction was significantly reduced, the number of surviving cell in the hippocampal CA1 region increased, the number of apoptotic cells decreased, the expression of caspase-3 and poly（adenosine diphosphate-ribose） polymerase-1 protein was down-regulated, and the escape latency in the water maze test was significantly shortened compared with the ischemia-reperfusion group. Our experimental findings indicate that minocycline can protect against neuronal injury induced by focal ischemia-reperfusion, which may be mediated by the inhibition of caspase-3 and poly（adenosine diphosphate-ribose） polymerase-1 protein expression.

Chloride channel blocker 4,4-diisothiocyanatostilbene-2,2'-disulfonic acid inhibits nitric oxide-induced apoptosis in cultured rat hippocampal neurons

Apoptosis in cultured rat hippocampal neurons was induced using the nitric oxide donor 3-morpholinosydnonimine, and cells were treated with the chloride channel blocker, 4,4- diisothiocyanatostilbene-2,2＇-disulfonic acid. Results showed that the survival rate of neurons was significantly increased after treatment with 4,4-diisothiocyanatostilbene-2,2＇-disulfonic acid, and the rate of apoptosis decreased. In addition, the expression of the apoptosis-related proteins poly（adenosine diphosphate-ribose）polymerase-1 and apoptosis-inducing factor were significantly reduced. Our experimental findings indicate that the chloride channel blocker 4,4- diisothiocyanatostilbene-2,2＇-disulfonic acid can antagonize apoptotic cell death of hippocampal neurons by inhibiting the expression of the apoptosis-related proteins poly（adenosine diphosphate-ribose）polymerase-1 and apoptosis-inducing factor.