• Biomolecules & Therapeutics
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• 제25권2호
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• pp.194-201
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• 2017

Lysophosphatidylethanolamine (LPE), a lyso-type metabolite of phosphatidylethanolamine, has been reported to be an intercellular signaling molecule. LPE mobilizes intracellular $Ca^{2+}$ through G-protein-coupled receptor (GPCR) in some cells types. However, GPCRs for lysophosphatidic acid (LPA) were not implicated in the LPE-mediated activities in LPA GPCR overexpression systems or in SK-OV3 ovarian cancer cells. In the present study, in human SH-SY5Y neuroblastoma cells, experiments with $LPA_1$ antagonists showed LPE induced intracellular $Ca^{2+}$ increases in an $LPA_1$ GPCR-dependent manner. Furthermore, LPE increased intracellular $Ca^{2+}$ through pertussis-sensitive G proteins, edelfosine-sensitive-phospholipase C, 2-APB-sensitive $IP_3$ receptors, $Ca^{2+}$ release from intracellular $Ca^{2+}$ stores, and subsequent $Ca^{2+}$ influx across plasma membranes, and LPA acted on $LPA_1$ and $LPA_2$ receptors to induce $Ca^{2+}$ response in a 2-APB-sensitive and insensitive manner. These findings suggest novel involvements for LPE and LPA in calcium signaling in human SH-SY5Y neuroblastoma cells.

• Biomolecules & Therapeutics
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• 제25권2호
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• pp.177-185
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• 2017

Auranofin has been developed as antirheumatic drugs, which is currently under clinical development for the treatment of chronic lymphocytic leukemia. Previous report showed that auranofin induced apoptosis by enhancement of annexin A5 expression in PC-3 cells. To understand the role of annexin A5 in auranofin-mediated apoptosis, we performed microarray data analysis to study annexin A5-controlled gene expression in annexin A5 knockdown PC-3 cells. Of differentially expressed genes, plasminogen activator inhibitor (PAI)-2 was increased by annexin A5 siRNA confirmed by qRT-PCR and western blot. Treatment with auranofin decreased PAI-2 and increased annexin A5 expression as well as promoting apoptosis. Furthermore, auranofin-induced apoptosis was recovered by annexin A5 siRNA but it was promoted by PAI-2 siRNA. Interestingly, knockdown of annexin A5 rescued PAI-2 expression suppressed by auranofin. Taken together, our study suggests that induction of annexin A5 by auranofin may enhance apoptosis through suppression of PAI-2 expression in PC-3 cells.

• 대한소화기학회지
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• 제72권5호
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• pp.237-244
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• 2018

While the prevalence of Helicobacter pylori (H. pylori) infection is decreasing in Korea, the incidence of gastric cancer remains high, emphasizing the importance of H. pylori eradication. A new treatment strategy is needed as the eradication rate with standard triple therapy, which is currently the standard first-line regimen for H. pylori infection, has decreased below the optimum level. The major cause of eradication failure is increased antibiotic resistance. Sequential, concurrent, and hybrid therapies that include clarithromycin produce higher eradication rates than conventional standard triple therapy. However, the effectiveness of these treatments is limited in regions where the resistance rate to various antibiotics is high. Bismuth quadruple therapy is another alternative therapy, but again the eradication rate is not sufficiently high. Tailored therapy based on individual characteristics, including antibiotic susceptibility, may be ideal, but there are several limitations for clinical application and further research is needed. New potassium-competitive acid blocker-based therapies could emerge as effective alternatives in the near future. A consensus is needed to establish a strategy for applying new eradication therapies in Korea.

• Biomolecules & Therapeutics
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• 제27권5호
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• pp.484-491
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• 2019

Glioblastoma is the most aggressive common brain tumor in adults. Curcumin, from Curcuma longa, is an effective antitumor agent. Although the same proteins control both autophagy and cell death, the molecular connections between them are complicated and autophagy may promote or inhibit cell death. We investigated whether curcumin affects autophagy, which regulates curcumin-mediated tumor cell death in A172 human glioblastoma cells. When A172 cells were incubated with $10{\mu}M$ curcumin, autophagy increased in a time-dependent manner. Curcumin-induced cell death was reduced by co-incubation with the autophagy inhibitors 3-methyladenine (3-MA), hydroxychloroquine (HCQ), and LY294002. Curcumin-induced cell death was also inhibited by co-incubation with rapamycin, an autophagy inducer. When cells were incubated under serum-deprived medium, LC3-II amount was increased but the basal level of cell viability was reduced, leading to the inhibition of curcumin-induced cell death. Cell death was decreased by inhibiting curcumin-induced autophagy using small interference RNA (siRNA) of Atg5 or Beclin1. Therefore, curcumin-mediated tumor cell death is promoted by curcumin-induced autophagy, but not by an increase in the basal level of autophagy in rapamycin-treated or serum-deprived conditions. This suggests that the antitumor effects of curcumin are influenced differently by curcumin-induced autophagy and the prerequisite basal level of autophagy in cancer cells.

• Journal of Plant Biotechnology
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• 제47권4호
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• pp.273-282
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• 2020

In Vietnam, Celastrus hindsii Benth, a medicinal plant rich in secondary metabolites, has been used to alleviate distress caused by ulcers, tumors, and inflammation for generations. The occurrence of two phenotypes, Broad Leaf (BL) and Narrow Leaf (NL), has raised questions about the selection of appropriate varieties for conservation and crop improvement to enhance medicinal properties. This study examined molecular differences in C. hindsii by comparing protein profiles between the NL and BL types using 2D-PAGE and MS. Peptide sequences and proteins were identified by matching MS data against the MSPnr100 databases and verified using the MultiIdent tool on ExPASy and the Blast2GO software. Our results revealed notable variations in protein abundance between the NL and BL proteomes. Selected proteins were confidently identified from 12 protein spots, thereby highlighting the molecular variation between NL and BL proteomes. Upregulated proteins in BL were found to be associated with flavonoid and amino acid biosynthesis as well as nuclease metabolism, which probably attributed to the intraspecific variations. Several bioactive proteins identified in this study can have applications in cancer therapeutics. Therefore, the BL phenotype characterized by healthier external morphological features has higher levels of bioactive compounds and could be better suited for medicinal use.

• 대한방사성의약품학회지
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• 제6권2호
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• pp.171-176
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• 2020

Covalent organic frameworks (COFs) are porous crystalline polymers in which organic units are linked by covalent bonds and have a regular arrangement at the atomic level. Recently, the COFs have been much attention in bio-medical area such as bio-imaging, drug delivery, and therapeutics. These 2D nanoparticles are proving their value in nanomedicine due to their large surface area, functionalization through functional groups exposed on the surface, chemical stability due to covalent bonding, and high biocompatibility. The high ω-electron density and crystallinity of COFs makes it a promising candidate for bioimaging probes, and its porosity and large surface area make it possible to be utilized as a drug delivery vehicle. However, the low dispersibility in water, the cytotoxicity problems of COFs are still challenged to be solved in the future. In this regard, several efforts that increase the degree of dispersion through functionalization on the surface of COFs for the application to the biomedical field have been reported. In this review, we would like to describe the advantages and limitations of COFs for bio-imaging and anti-cancer treatment.

• Biomolecules & Therapeutics
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• 제31권1호
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• pp.48-58
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• 2023

Interferon regulatory factor 3 (IRF3) integrates both immunological and non-immunological inputs to control cell survival and death. Small GTPases are versatile functional switches that lie on the very upstream in signal transduction pathways, of which duration of activation is very transient. The large number of homologous proteins and the requirement for site-directed mutagenesis have hindered attempts to investigate the link between small GTPases and IRF3. Here, we constructed a constitutively active mutant expression library for small GTPase expression using Gibson assembly cloning. Small-scale screening identified multiple GTPases capable of promoting IRF3 phosphorylation. Intriguingly, 27 of 152 GTPases, including ARF1, RHEB, RHEBL1, and RAN, were found to increase IRF3 phosphorylation. Unbiased screening enabled us to investigate the sequence-activity relationship between the GTPases and IRF3. We found that the regulation of IRF3 by small GTPases was dependent on TBK1. Our work reveals the significant contribution of GTPases in IRF3 signaling and the potential role of IRF3 in GTPase function, providing a novel therapeutic approach against diseases with GTPase overexpression or active mutations, such as cancer.

• 멤브레인
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• 제34권2호
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• pp.124-131
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• 2024

바이러스는 생물 의약 산업에서 다양한 응용 분야를 가지고 있다. 그들은 살충제 생산, 백신 생산, 유전자 전달, 암 치료제 등에 사용된다. 바이러스의 하류 처리는 그들의 생물학적 및 의약적 응용을 위한 필수 단계이다. 다양한 과정 중에서 바이러스의 정제는 매우 중요하다. 막 크로마토그래피는 이 과정에서 중요한 역할을 한다. 이온 교환 막 크로마토그래피는 주로 사용되는 방법이지만 크기 배제 및 불충분한 정제에 관한 다양한 제한을 가지고 있다. 또한, 이는 인플루엔자와 같은 빠르게 변화하는 바이러스의 균주에 적용될 수 없다. 이 검토는 막 크로마토그래피의 다양한 개선된 방법 또는 대안을 검토한다. 이는 정제, 바이러스 회수율 및 방법의 확장성에 초점을 맞추고 있다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권16호
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• pp.7071-7076
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• 2015

Epidermal growth factor receptor (EGFR) is one of the targeted molecular markers in many cancers including lung malignancies. Gefitinib and erlotinib are two available therapeutics that act as specific inhibitors of tyrosine kinase (TK) domains. We performed a case-control study with formalin-fixed paraffin-embedded tissue blocks (FFPE) from tissue biopsies of 167 non-small cell lung carcinoma (NSCLC) patients and 167 healthy controls. The tissue biopsies were studied for mutations in exons 18-21 of the EGFR gene. This study was performed using PCR followed by DNA sequencing. We identified 63 mutations in 33 men and 30 women. Mutations were detected in exon 19 (delE746-A750, delE746-T751, delL747-E749, delL747-P753, delL747-T751) in 32 patients, exon 20 (S786I, T790M) in 16, and exon 21 (L858R) in 15. No mutations were observed in exon 18. The 63 patients with EFGR mutations were considered for upfront therapy with oral tyrosine kinase inhibitor (TKI) drugs and have responded well to therapy over the last 15 months. The control patients had no mutations in any of the exons studied. The advent of EGFR TKI therapy has provided a powerful new treatment modality for patients diagnosed with NSCLC. The study emphasizes the frequency of EGFR mutations in NSCLC patients and its role as an important predictive marker for response to oral TKI in the south Indian population.

• Biomolecules & Therapeutics
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• 제25권5호
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• pp.545-552
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• 2017

Increasing concern is being given to the association between risk of cancer and exposure to low-dose bisphenol A (BPA), especially in young-aged population. In this study, we investigated the effects of repeated oral treatment of low to high dose BPA in juvenile Sprague-Dawley rats. Exposing juvenile rats to BPA (0, 0.5, 5, 50, and 250 mg/kg oral gavage) from post-natal day 9 for 90 days resulted in higher food intakes and increased body weights in biphasic dose-effect relationship. Male mammary glands were atrophied at high dose, which coincided with sexual pre-maturation of females. Notably, proliferative changes with altered cell foci and focal inflammation were observed around bile ducts in the liver of all BPA-dosed groups in males, which achieved statistical significance from 0.5 mg/kg (ANOVA, Dunnett's test, p<0.05). Toxicokinetic analysis revealed that systemic exposure to BPA was greater at early age (e.g., 210-fold in $C_{max}$, and 26-fold in AUC at 50 mg/kg in male on day 1 over day 90) and in females (e.g., 4-fold in $C_{max}$ and 1.6-fold in AUC at 50 mg/kg vs. male on day 1), which might have stemmed from either age- or gender-dependent differences in metabolic capacity. These results may serve as evidence for the association between risk of cancer and exposure to low-dose BPA, especially in young children, as well as for varying toxicity of xenobiotics in different age and gender groups.