• BMB Reports
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• 제36권1호
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• pp.144-148
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• 2003

During the past 2 decades, radiation tumorigenesis researchers have focused on cellular and molecular mechanisms. We reviewed some of these research fields, since they may specifically relate to the induction of cancer by ionizing radiation. First, radiation-mediated mutation was discussed. Then the initiating event in radiation carcinogenesis, as well as other genetic events that may by involved, is discussed in terms of the possible role of the activation of genes and the loss of cell-cycle checkpoints.

• Molecules and Cells
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• 제39권1호
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• pp.72-76
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• 2016

Cell death pathways such as apoptosis can be activated in response to oxidative stress, enabling the disposal of damaged cells. In contrast, controlled intracellular redox events are proposed to be a significant event during apoptosis signaling, regardless of the initiating stimulus. In this scenario oxidants act as second messengers, mediating the post-translational modification of specific regulatory proteins. The exact mechanism of this signaling is unclear, but increased understanding offers the potential to promote or inhibit apoptosis through modulating the redox environment of cells. Peroxiredoxins are thiol peroxidases that remove hydroperoxides, and are also emerging as important players in cellular redox signaling. This review discusses the potential role of peroxiredoxins in the regulation of apoptosis, and also their ability to act as biomarkers of redox changes during the initiation and progression of cell death.

• Journal of Ginseng Research
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• 제44권3호
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• pp.461-474
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• 2020

Background: Ginseng effectively reduces fatigue in both animal models and clinical trials. However, the mechanism of action is not completely understood, and its molecular targets remain largely unknown. Methods: By screening for proteins that interact with the primary components of ginseng (ginsenosides) in an affinity chromatography assay, we have identified muscle-type creatine kinase (CK-MM) as a potential target in skeletal muscle tissues. Results: Biolayer interferometry analysis showed that ginsenoside metabolites, instead of parent ginsenosides, had direct interaction with recombinant human CK-MM. Subsequently, 20(S)-protopanaxadiol (PPD), which is a ginsenoside metabolite and displayed the strongest interaction with CK-MM in the study, was selected as a representative to confirm direct binding and its biological importance. Biolayer interferometry kinetics analysis and isothermal titration calorimetry assay demonstrated that PPD specifically bound to human CK-MM. Moreover, the mutation of key amino acids predicted by molecular docking decreased the affinity between PPD and CK-MM. The direct binding activated CK-MM activity in vitro and in vivo, which increased the levels of tissue phosphocreatine and strengthened the function of the creatine kinase/phosphocreatine system in skeletal muscle, thus buffering cellular ATP, delaying exercise-induced lactate accumulation, and improving exercise performance in mice. Conclusion: Our results suggest a cellular target and an initiating molecular event by which ginseng reduces fatigue. All these findings indicate PPD as a small molecular activator of CK-MM, which can help in further developing better CK-MM activators based on the dammarane-type triterpenoid structure.

• Asian Pacific Journal of Cancer Prevention
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• 제16권5호
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• pp.1945-1952
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• 2015

Inflammatory bowel disease (IBD) is a disease strongly associated with colorectal cancer (CRC) as a well-known precancerous condition. Alterations in DNA methylation and mutation in K-ras are believed to play an early etiopathogenic role in CRC and may also an initiating event through deregulation of molecular signaling. Epigenetic silencing of APC and SFRP2 in the WNT signaling pathway may also be involved in IBD-CRC. The role of aberrant DNA methylation in precancerous state of colorectal cancer (CRC) is under intensive investigation worldwide. The aim of this study was to investigate the status of promoter methylation of MGMT-B, APC1A and SFRP2 genes, in inflamed and normal colon tissues of patients with IBD compared with control normal tissues. A total of 52 IBD tissues as well as corresponding normal tissues and 30 samples from healthy participants were obtained. We determined promoter methylation status of MGMT-B, SFRP2 and APC1A genes by chemical treatment with sodium bisulfite and subsequent MSP. The most frequently methylated locus was MGMT-B (71%; 34 of 48), followed by SFRP2 (66.6 %; 32 of 48), and APC1A (43.7%; 21 of 48). Our study demonstrated for the first time that hypermethylation of the MGMT-B and the SFRP2 gene promoter regions might be involved in IBD development. Methylation of MGMT-B and SFRP2 in IBD patients may provide a method for early detection of IBD-associated neoplasia.

• 한국산업보건학회지
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• 제29권2호
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• pp.141-158
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• 2019

Objectives: An adverse outcome pathway is a biological pathway that disturbs homeostasis and causes toxicity. It is a conceptual framework for organizing existing biological knowledge and consists of the molecular initiating event, key event, and adverse output. The AOP concept provides intuitive risk identification that can be helpful in evaluating the carcinogenicity of chemicals and in the prevention of cancer through the assessment of chemical carcinogenicity predictions. Methods: We reviewed various papers and books related to the application of AOPs for the prevention of occupational cancer. We mainly used the internet to search for the necessary research data and information, such as via Google scholar(http://scholar.google.com), ScienceDirect(www.sciencedirect.com), Scopus(www.scopus. com), NDSL(http: //www.ndsl.kr/index.do) and PubMed(http://www.ncbi.nlm.nih.gov/pubmed). The key terms searched were "adverse outcome pathway," "toxicology," "risk assessment," "human exposure," "worker," "nanoparticle," "applications," and "occupational safety and health," among others. Results: Since it focused on the current state of AOP for the prediction of toxicity from chemical exposure at work and prospects for industrial health in the context of the AOP concept, respiratory and nanomaterial hazard assessments. AOP provides an intuitive understanding of the toxicity of chemicals as a conceptual means, and it works toward accurately predicting chemical toxicity. The AOP technique has emerged as a future-oriented alternative to the existing paradigm of chemical hazard and risk assessment. AOP can be applied to the assessment of chemical carcinogenicity along with efforts to understand the effects of chronic toxic chemicals in workplaces. Based on these predictive tools, it could be possible to bring about a breakthrough in the prevention of occupational and environmental cancer. Conclusions: The AOP tool has emerged as a future-oriented alternative to the existing paradigm of chemical hazard and risk assessment and has been widely used in the field of chemical risk assessment and the evaluation of carcinogenicity at work. It will be a useful tool for prediction, and it is possible that it can help bring about a breakthrough in the prevention of occupational and environmental cancer.