• Journal of Life Science
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• v.33 no.6
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• pp.523-529
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• 2023

Ubiquitination is a post-translational modification that is involved in the quality control of proteins and responsible for modulating a variety of cellular physiological processes. Protein ubiquitination and deubiquitination are reversible processes that regulate the stability of target substrates. The ubiquitin proteasome system (UPS) helps regulate tumor-promoting processes, such as DNA repair, cell cycle, apoptosis, metastasis, and angiogenesis. The UPS comprises a combination of ubiquitin, ubiquitin-activating enzymes (E1), ubiquitin-conjugating enzymes (E2), and ubiquitin-ligase enzymes (E3), which complete the degradation of target proteins. Ubiquitin-conjugating enzymes (UBE2s) play an inter-mediate role in the UPS process by moving activated ubiquitin to target proteins through E3 ligases. UBE2s consist of 40 members and are classified according to conserved catalytic ubiquitin-conjugating (UBC) domain-flanking extensions in humans. Since UBE2s have specificity to substrates like E3 ligase, the significance of UBE2 has been accentuated in tumorigenesis. The dysregulation of multiple E2 enzymes and their critical roles in modulating oncogenic signaling pathways have been reported in several types of cancer. The elevation of UBE2 expression is correlated with a worse prognosis in cancer patients. In this review, we summarize the basic functions and regulatory mechanisms of UBE2s and suggest the possibility of their use as therapeutic targets for cancer.

• Tuberculosis and Respiratory Diseases
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• v.53 no.5
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• pp.485-496
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• 2002

Background : Nonsteroidal anti-inflammatory drugs (NSAIDs) are useful in the chemoprevention of colon cancers. Continuous NSAID use results in a 40% to 50% reduction in the relative risk of colorectal cancer. The precise mechanism by which NSAIDs prevent and/or cause the regression of colorectal tumors is not known. Some investigators have reported that certain NSAIDs induce apoptosis and alter the expression of the cell cycle regulatory genes in some carcinoma cells when administered at a relatively high concentration. However, the possibility of NSAIDs application as chemopreventive agents in lung cancers remains to be elucidated. To address this question, the human lung cancer cell line NCI-H1299 was used to investigate whether or not NSAIDs might induce the apoptotic death of NCI-H1299 cells. Methods : A viability test was carried out using a MTT assay. Apoptosis was measured by flow cytometric analysis and unclear staining(DAPI). The talytic activity of the caspase family was measured by the fluirigenic cleavage of biosubstrates. To define the mechanical basis of apoptosis, western blot was performed to analyze the expression of the death substrates(PARP and ICAD). Results : NaSaL significantly decreased the viability of the NCI-H1299 cells, which was revealed as apoptosis characterized by an increase in the $subG_0/G_1$ population and unclear fragmentation. The catalytic activity of caspase-3 protease began to increase after 24 Hr and reached a peak 30 Hr after treatment with 10 mM NaSaL. In contrast, caspase-6, 8, and 9 proteases did not have a significantly altered enzymatic activity. Consistent with activation of caspase-3 protease, NaSaL induced the cleavage of the protease biosubstrate. Conclusion : NaSaL induces the apoptotic death of NCI-H1299 human lung cancer cells via the activation of caspase-3 protease.

• Clinical and Experimental Pediatrics
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• v.52 no.2
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• pp.213-219
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• 2009

Purpose:Iron is a critical nutritional element that is essential for a variety of important biological processes, including cell growth and differentiation, electron transfer reactions, and oxygen transport, activation, and detoxification. Iron is also required for neoplastic cell growth due to its catalytic effects on the formation of hydroxyl radicals, suppression of host defense cell activities, and promotion of cancer cell multiplication. Chronic transfusion-dependent patients receiving chemotherapy may have iron overload, which requires iron-chelating therapy. We performed this study to demonstrate whether the iron chelating agent deferoxamine induces apoptosis in Saos-2 osteosarcoma cells, and to investigate the underlying apoptotic mechanism. Methods:To analyze the apoptotic effects of an iron chelator, cultured Saos-2 cells were treated with deferoxamine. We analyzed cell survival by trypan blue and crystal violet analysis, apoptosis by nuclear condensation, DNA fragmentation, and cell cycle analysis, and the expression of apoptotic related proteins by Western immunoblot analysis. Results:Deferoxamine inhibited the growth of Saos-2 cell in a time- and dose-dependent manner. The major mechanism for growth inhibition with the deferoxamine treatment was by the induction of apoptosis, which was supported by nuclear staining, DNA fragmentation analysis, and flow cytometric analysis. Furthermore, bcl-2 expression decreased, while bax, caspase-3, caspase-9, and PARP expression increased in Saos-2 cells treated with deferoxamine. Conclusion:These results demonstrated that the iron chelating agent deferoxamine induced growth inhibition and mitochondrial-dependent apoptosis in osteosarcoma Saos-2 cells, suggesting that iron chelating agents used in controlling neoplastic cell fate can be potentially developed as an adjuvant agent enhancing the anti-tumor effect for the treatment of osteosarcoma.