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Article ; Online: CX-4945 (Silmitasertib) Induces Cell Death by Impairing Lysosomal Utilization in

Lee, DA Sol / Han, Min Woo / Kang, Yonghyun / Kim, Chorong / Lee, Seonmin / Kim, Kyu-Pyo / Yoo, Changhoon

2024 Volume 44, Issue 5, Page(s) 1939–1946

Abstract: Background/aim: Macropinocytosis is a non-selective form of endocytosis that facilitates the uptake of extracellular substances, such as nutrients and macromolecules, into the cells. In KRAS-driven cancers, including pancreatic ductal adenocarcinoma, ... ...

Abstract	Background/aim: Macropinocytosis is a non-selective form of endocytosis that facilitates the uptake of extracellular substances, such as nutrients and macromolecules, into the cells. In KRAS-driven cancers, including pancreatic ductal adenocarcinoma, macropinocytosis and subsequent lysosomal utilization are known to be enhanced to overcome metabolic stress. In this study, we investigated the role of Casein Kinase 2 (CK2) inhibition in macropinocytosis and subsequent metabolic processes in KRAS mutant cholangiocarcinoma (CCA) cell lines. Materials and methods: The bovine serum albumin (BSA) uptake indicating macropinocytosis was performed by flow cytometry using the HuCCT1 KRAS mutant CCA cell line. To validate macropinosome, the Rab7 and LAMP2 were labeled and analyzed via immunocytochemistry and western blot. The CX-4945 (Silmitasertib), CK2 inhibitor, was used to investigate the role of CK2 in macropinocytosis and subsequent lysosomal metabolism. Results: The TFK-1, a KRAS wild-type CCA cell line, showed only apoptotic morphological changes. However, the HuCCT1 cell line showed macropinocytosis. Although CX-4945 induced morphological changes accompanied by the accumulation of intracellular vacuoles and cell death, the level of macropinocytosis did not change. These intracellular vacuoles were identified as late macropinosomes, representing Rab7+ vesicles before fusion with lysosomes. In addition, CX-4945 suppressed LAMP2 expression following the inhibition of the Akt-mTOR signaling pathway, which interrupts mature macropinosome and lysosomal metabolic utilization. Conclusion: Macropinocytosis is used as an energy source in the KRAS mutant CCA cell line HuCCT1. The inhibition of CK2 by CX-4945 leads to cell death in HuCCT1 cells through alteration of the lysosome-dependent metabolism.
MeSH term(s)	Humans ; Lysosomes/metabolism ; Cell Line, Tumor ; Cholangiocarcinoma/pathology ; Cholangiocarcinoma/metabolism ; Cholangiocarcinoma/genetics ; Pinocytosis/drug effects ; Proto-Oncogene Proteins p21(ras)/genetics ; Proto-Oncogene Proteins p21(ras)/metabolism ; Casein Kinase II/metabolism ; Casein Kinase II/genetics ; Casein Kinase II/antagonists & inhibitors ; Piperazines/pharmacology ; Mutation ; Bile Duct Neoplasms/pathology ; Bile Duct Neoplasms/metabolism ; Bile Duct Neoplasms/genetics ; rab7 GTP-Binding Proteins/metabolism ; Cell Death/drug effects ; Apoptosis/drug effects ; Lysosomal-Associated Membrane Protein 2/metabolism ; Lysosomal-Associated Membrane Protein 2/genetics ; rab GTP-Binding Proteins/metabolism ; rab GTP-Binding Proteins/genetics ; Naphthyridines ; Phenazines
Chemical Substances	silmitasertib (C6RWP0N0L2) ; KRAS protein, human ; Proto-Oncogene Proteins p21(ras) (EC 3.6.5.2) ; Casein Kinase II (EC 2.7.11.1) ; Piperazines ; rab7 GTP-Binding Proteins ; rab7 GTP-binding proteins, human ; LAMP2 protein, human ; Lysosomal-Associated Membrane Protein 2 ; rab GTP-Binding Proteins (EC 3.6.5.2) ; Naphthyridines ; Phenazines
Language	English
Publishing date	2024-04-27
Publishing country	Greece
Document type	Journal Article
ZDB-ID	604549-2
ISSN	1791-7530 ; 0250-7005
ISSN (online)	1791-7530
ISSN	0250-7005
DOI	10.21873/anticanres.16996
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: S-Nitrosoglutathione (GSNO)-Mediated Lead Detoxification in Soybean through the Regulation of ROS and Metal-Related Transcripts.

Methela, Nusrat Jahan / Islam, Mohammad Shafiqul / Lee, Da-Sol / Yun, Byung-Wook / Mun, Bong-Gyu

International journal of molecular sciences

2023 Volume 24, Issue 12

Abstract: Heavy metal toxicity, including lead (Pb) toxicity, is increasing in soils, and heavy metals are considered to be toxic in small amounts. Pb contamination is mainly caused by industrialization (e.g., smelting and mining), agricultural practices (e.g., ... ...

Abstract	Heavy metal toxicity, including lead (Pb) toxicity, is increasing in soils, and heavy metals are considered to be toxic in small amounts. Pb contamination is mainly caused by industrialization (e.g., smelting and mining), agricultural practices (e.g., sewage sludge and pests), and urban practices (e.g., lead paint). An excessive concentration of Pb can seriously damage and threaten crop growth. Furthermore, Pb adversely affects plant growth and development by affecting the photosystem, cell membrane integrity, and excessive production of reactive oxygen species (ROS) such as hydrogen peroxide (H
MeSH term(s)	Reactive Oxygen Species/metabolism ; S-Nitrosoglutathione/metabolism ; Glycine max/metabolism ; Hydrogen Peroxide/metabolism ; Lead/toxicity ; Lead/metabolism ; Metals, Heavy/metabolism ; Antioxidants/metabolism ; Plants/metabolism ; Nitric Oxide/metabolism ; Heavy Metal Poisoning
Chemical Substances	Reactive Oxygen Species ; S-Nitrosoglutathione (57564-91-7) ; Hydrogen Peroxide (BBX060AN9V) ; Lead (2P299V784P) ; Metals, Heavy ; Antioxidants ; Nitric Oxide (31C4KY9ESH)
Language	English
Publishing date	2023-06-08
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24129901
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Article ; Online: PARP Inhibitor Sensitizes

Kim, Chorong / Kim, Danbee / Lee, DA Sol / Lee, Seonmin / Yoo, Changhoon / Kim, Kyu-Pyo

Anticancer research

2023 Volume 43, Issue 12, Page(s) 5523–5534

Abstract: Background/aim: Currently, olaparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, has been approved as maintenance therapy for patients with germline BRCA mutations and metastatic pancreatic cancer. However, platinum-based chemotherapy, which induces ...

Abstract	Background/aim: Currently, olaparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, has been approved as maintenance therapy for patients with germline BRCA mutations and metastatic pancreatic cancer. However, platinum-based chemotherapy, which induces synthetic lethality with PARP inhibitor treatment, is still controversial. Hence, we aimed to examine a platinum-based drug in combination with a PARP inhibitor and generate data regarding the use of a PARP inhibitor in the overall treatment of pancreatic cancer. Materials and methods: Using the Capan-1 cell line (BRCA2-mutant pancreatic cancer cell line), we evaluated the combinatorial effects of olaparib, a PARP inhibitor, and oxaliplatin by cell viability, combination index, western blotting, immunocytochemistry, flow cytometry, apoptosis assays and in vivo experiments. Results: Capan-1 cells showed high sensitivity to olaparib due to the alteration in PARP activity, which led to cell death through the accumulation of oxaliplatin-induced DNA damage. Beyond DNA damage, oxaliplatin also suppressed the CDK1/BRCA1 signaling axis, which induced defects in homologous recombination repair. Additionally, inhibition of CDK1, a biomarker for oxaliplatin efficacy, induced cell death regardless of the BRCA mutation profile. Conclusion: Oxaliplatin may be used in combination with olaparib in PDAC patients with DNA damage repair mutations. Our findings highlight CDK1 as a potential therapeutic target for pancreatic cancer.
MeSH term(s)	Humans ; Poly(ADP-ribose) Polymerase Inhibitors/pharmacology ; Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use ; Oxaliplatin/pharmacology ; DNA Repair ; DNA Damage ; Poly(ADP-ribose) Polymerases/metabolism ; Pancreatic Neoplasms/drug therapy ; Pancreatic Neoplasms/genetics ; Phthalazines/pharmacology ; Phthalazines/therapeutic use ; BRCA1 Protein/genetics ; BRCA1 Protein/metabolism ; CDC2 Protein Kinase/metabolism
Chemical Substances	Poly(ADP-ribose) Polymerase Inhibitors ; Oxaliplatin (04ZR38536J) ; Poly(ADP-ribose) Polymerases (EC 2.4.2.30) ; Phthalazines ; BRCA1 protein, human ; BRCA1 Protein ; CDK1 protein, human (EC 2.7.11.22) ; CDC2 Protein Kinase (EC 2.7.11.22)
Language	English
Publishing date	2023-11-29
Publishing country	Greece
Document type	Journal Article
ZDB-ID	604549-2
ISSN	1791-7530 ; 0250-7005
ISSN (online)	1791-7530
ISSN	0250-7005
DOI	10.21873/anticanres.16754
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 1642: Show issues

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ab Jg. 2022: Lesesaal (EG)

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Article ; Online: The Casein Kinase 2 Inhibitor CX-4945 Promotes Cholangiocarcinoma Cell Death Through PLK1.

Lee, DA Sol / Lee, Seonmin / Kim, Chorong / Kim, Danbee / Kim, Kyu-Pyo / Yoo, Changhoon

Anticancer research

2022 Volume 42, Issue 7, Page(s) 3435–3443

Abstract: Background/aim: Casein Kinase 2 (CK2) is a prosurvival protein kinase involved in cell growth/proliferation through the regulation of the cell cycle and apoptosis. CK2 is over-expressed in various cancers, which correlates with a poor prognosis. This ... ...

Abstract	Background/aim: Casein Kinase 2 (CK2) is a prosurvival protein kinase involved in cell growth/proliferation through the regulation of the cell cycle and apoptosis. CK2 is over-expressed in various cancers, which correlates with a poor prognosis. This study examined the anti-cancer effects of silmitasertib (CX-4945), a CK2 inhibitor, on cholangiocarcinoma (CCA) cells. Materials and methods: The effects of CX-4945 on cell viability, cell cycle arrest, and apoptosis in the human cholangiocarcinoma cell lines TFK-1 and SSP-25 were evaluated. Alterations in posttranslational modifications and the levels of cell cycle regulators including p21, Polo-like kinase 1 (PLK1), andp53 were assessed by western blotting. Apoptotic responses were examined using Propidium iodine/Annexin V staining. Results: TFK-1 and SSP-25 cells exposed to CX-4945 showed morphologic changes and a more than 50% decrease in cell viability (p<0.05). Cell cycle arrest at the G2 phase was detected following an increase in phosphorylated PLK1 and p21. Furthermore, phospho-PLK1 induced the degradation of p53, which led to the dissociation of Bax from Bcl-xL. The cleavage of Caspase3 and PARP were also induced by CX-4945 treatment. Conclusion: CX-4945 induces cell cycle arrest and cell death in cholangiocarcinoma cells via the regulation of PLK1 and p53. This may provide a novel therapeutic strategy for advanced cholangiocarcinoma.
MeSH term(s)	Bile Duct Neoplasms/drug therapy ; Bile Ducts, Intrahepatic ; Casein Kinase II ; Cell Cycle Proteins ; Cell Death ; Cholangiocarcinoma/drug therapy ; Humans ; Naphthyridines ; Phenazines ; Protein Serine-Threonine Kinases ; Proto-Oncogene Proteins ; Tumor Suppressor Protein p53 ; Polo-Like Kinase 1
Chemical Substances	Cell Cycle Proteins ; Naphthyridines ; Phenazines ; Proto-Oncogene Proteins ; Tumor Suppressor Protein p53 ; silmitasertib (C6RWP0N0L2) ; Casein Kinase II (EC 2.7.11.1) ; Protein Serine-Threonine Kinases (EC 2.7.11.1)
Language	English
Publishing date	2022-06-25
Publishing country	Greece
Document type	Journal Article
ZDB-ID	604549-2
ISSN	1791-7530 ; 0250-7005
ISSN (online)	1791-7530
ISSN	0250-7005
DOI	10.21873/anticanres.15830
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Exogenous SA Applications Alleviate Salinity Stress via Physiological and Biochemical changes in St John's Wort Plants.

Kwon, Eun-Hae / Adhikari, Arjun / Imran, Muhammad / Lee, Da-Sol / Lee, Chung-Yeol / Kang, Sang-Mo / Lee, In-Jung

Plants (Basel, Switzerland)

2023 Volume 12, Issue 2

Abstract: The plant St. John's wort contains high levels of melatonin, an important biochemical that has both beneficial and adverse effects on stress. Therefore, a method for increasing melatonin levels in plants without adversely affecting their growth is ... ...

Abstract	The plant St. John's wort contains high levels of melatonin, an important biochemical that has both beneficial and adverse effects on stress. Therefore, a method for increasing melatonin levels in plants without adversely affecting their growth is economically important. In this study, we investigated the regulation of melatonin levels in St. John's wort by exposing samples to salinity stress (150 mM) and salicylic acid (0.25 mM) to augment stress tolerance. The results indicated that salinity stress significantly reduced the plant chlorophyll content and damaged the photosystem, plant growth and development. Additionally, these were reconfirmed with biochemical indicators; the levels of abscisic acid (ABA) and proline were increased and the activities of antioxidants were reduced. However, a significant increase was found in melatonin content under salinity stress through upregulation in the relative expression of tryptophan decarboxylase (
Language	English
Publishing date	2023-01-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2704341-1
ISSN	2223-7747
ISSN	2223-7747
DOI	10.3390/plants12020310
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Article ; Online: Correction to "Discovery and Feasibility Study of Medical Fluorophore 33 as a Novel Theranostic Agent".

Son, Kwang Hee / Lee, Da Sol / Park, Geumi / Jeon, So Yeon / Lee, Jae-Eon / Jeon, Hui-Jeon / Lee, Sijoon / Park, Woo-Jin / Shin, Yeonju / Kim, Seong Gon / Lee, Dong-Seok / Han, Ye Ri / Kim, Dong-Su / Jeon, Yong Hyun

ACS applied materials & interfaces

2024 Volume 16, Issue 13, Page(s) 17062

Language	English
Publishing date	2024-03-21
Publishing country	United States
Document type	Published Erratum
ISSN	1944-8252
ISSN (online)	1944-8252
DOI	10.1021/acsami.4c03839
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Article ; Online: Chitosan-GSNO nanoparticles: a positive modulator of drought stress tolerance in soybean.

Methela, Nusrat Jahan / Pande, Anjali / Islam, Mohammad Shafiqul / Rahim, Waqas / Hussain, Adil / Lee, Da-Sol / Mun, Bong-Gyu / Maria Joseph Raj, Nirmal Prashanth / Kim, Sang-Jae / Kim, Yoonha / Yun, Byung-Wook

BMC plant biology

2023 Volume 23, Issue 1, Page(s) 639

Abstract: Background: Chitosan biopolymer is an emerging non-toxic and biodegradable plant elicitor or bio-stimulant. Chitosan nanoparticles (CSNPs) have been used for the enhancement of plant growth and development. On the other hand, NO is an important ... ...

Abstract	Background: Chitosan biopolymer is an emerging non-toxic and biodegradable plant elicitor or bio-stimulant. Chitosan nanoparticles (CSNPs) have been used for the enhancement of plant growth and development. On the other hand, NO is an important signaling molecule that regulates several aspects of plant physiology under normal and stress conditions. Here we report the synthesis, characterization, and use of chitosan-GSNO nanoparticles for improving drought stress tolerance in soybean. Results: The CSGSNONPs released NO gas for a significantly longer period and at a much lower rate as compared to free GSNO indicating that incorporation of GSNO in CSNPs can protect the NO-donor from rapid decomposition and ensure optimal NO release. CS-GSNONPs improved drought tolerance in soybean plants reflected by a significant increase in plant height, biomass, root length, root volume, root surface area, number of root tips, forks, and nodules. Further analyses indicated significantly lower electrolyte leakage, higher proline content, higher catalase, and ascorbate peroxidase activity, and reduction in MDA and H Conclusions: This study highlights the potential of nano-technology-based delivery systems for nitric oxide donors to improve plant growth, and development and protect against stresses.
MeSH term(s)	Droughts ; Drought Resistance ; Glycine max/genetics ; Chitosan ; Hydrogen Peroxide/metabolism ; Nanoparticles ; Stress, Physiological/genetics
Chemical Substances	Chitosan (9012-76-4) ; Hydrogen Peroxide (BBX060AN9V)
Language	English
Publishing date	2023-12-11
Publishing country	England
Document type	Journal Article
ZDB-ID	2059868-3
ISSN	1471-2229 ; 1471-2229
ISSN (online)	1471-2229
ISSN	1471-2229
DOI	10.1186/s12870-023-04640-x
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Article: Enhanced Resistance of

Al Azzawi, Tiba Nazar / Khan, Murtaza / Mun, Bong-Gyu / Lee, Sang-Uk / Imran, Muhammad / Hussain, Adil / Rolly, Nkulu Kabange / Lee, Da-Sol / Ali, Sajid / Lee, In-Jung / Yun, Byung-Wook

Antioxidants (Basel, Switzerland)

2023 Volume 12, Issue 5

Abstract: Nitric oxide (NO) regulates several biological and physiological processes in plants. This study investigated the role ... ...

Abstract	Nitric oxide (NO) regulates several biological and physiological processes in plants. This study investigated the role of
Language	English
Publishing date	2023-04-24
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2704216-9
ISSN	2076-3921
ISSN	2076-3921
DOI	10.3390/antiox12050989
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Article ; Online: Epithelial-Mesenchymal Transition Phenotype and Peritumoral Immune Cell Infiltration in Advanced Biliary Tract Cancer.

Oh, Chung Ryul / Kim, Hyung-Don / Ryu, Yeon-Mi / Lee, Seonmin / Kim, Danbee / Lee, DA Sol / Jeong, Jae Ho / Chang, Heung-Moon / Ryoo, Baek-Yeol / Kim, Kyu-Pyo / Kim, Miyeon / Kim, Sang-Yeob / Yoo, Changhoon

Anticancer research

2023 Volume 43, Issue 2, Page(s) 645–652

Abstract: Background/aim: This study evaluated the clinical implications of epithelial-mesenchymal transition (EMT) markers and peritumoral immune cell infiltration in patients with biliary tract cancer (BTC) treated with gemcitabine plus cisplatin (GemCis).: ... ...

Abstract	Background/aim: This study evaluated the clinical implications of epithelial-mesenchymal transition (EMT) markers and peritumoral immune cell infiltration in patients with biliary tract cancer (BTC) treated with gemcitabine plus cisplatin (GemCis). Materials and methods: Forty-five patients with advanced BTC who received GemCis were included as the study population. We conducted multiplex immunohistochemistry and examined EMT markers and their correlations with immune cell infiltrate at the invasive tumor margin. Study population was subdivided into two groups: twenty-four patients with overall survival (OS) less than 10 months (short-term survivor group, SS) and 21 with OS of 20 months or longer (long-term survivor group, LS). Results: The density of tumor cells expressing epithelial marker E-cadherin (E-cadherin Conclusion: EMT-related features were enriched in BTC patients with poor survival outcomes and associated with regulatory T-cell infiltration.
MeSH term(s)	Humans ; Epithelial-Mesenchymal Transition/genetics ; Vimentin/genetics ; Cadherins/genetics ; Bile Duct Neoplasms/drug therapy ; Biliary Tract Neoplasms/pathology ; Deoxycytidine/therapeutic use ; Phenotype ; Biomarkers, Tumor
Chemical Substances	Vimentin ; Cadherins ; Deoxycytidine (0W860991D6) ; Biomarkers, Tumor
Language	English
Publishing date	2023-01-25
Publishing country	Greece
Document type	Journal Article
ZDB-ID	604549-2
ISSN	1791-7530 ; 0250-7005
ISSN (online)	1791-7530
ISSN	0250-7005
DOI	10.21873/anticanres.16201
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Enhanced Resistance of atnigr1 against Pseudomonas syringae pv. tomato Suggests Negative Regulation of Plant Basal Defense and Systemic Acquired Resistance by AtNIGR1 Encoding NAD(P)-Binding Rossmann-Fold in Arabidopsis thaliana

Al Azzawi, Tiba Nazar / Khan, Murtaza / Mun, Bong-Gyu / Lee, Sang Uk / Imran, Muhammad / Hussain, Adil / Rolly, Nkulu Kabange / Lee, Da-Sol / ʻAlī, Sājid / Lee, In-Jung / Yun, Byung-Wook

Antioxidants. 2023 Apr. 24, v. 12, no. 5

2023

Abstract: Nitric oxide (NO) regulates several biological and physiological processes in plants. This study investigated the role of Arabidopsis thaliana Negative Immune and Growth Regulator 1 (AtNIGR1), encoding an NAD(P)-binding Rossmann-fold superfamily, in the ... ...

Abstract	Nitric oxide (NO) regulates several biological and physiological processes in plants. This study investigated the role of Arabidopsis thaliana Negative Immune and Growth Regulator 1 (AtNIGR1), encoding an NAD(P)-binding Rossmann-fold superfamily, in the growth and immunity of Arabidopsis thaliana. AtNIGR1 was pooled from the CySNO transcriptome as a NO-responsive gene. Seeds of the knockout (atnigr1) and overexpression plants were evaluated for their response to oxidative [(hydrogen peroxide (H₂O₂) and methyl viologen (MV)] or nitro-oxidative [(S-nitroso-L-cysteine (CySNO) and S-nitroso glutathione (GSNO)] stress. Results showed that the root and shoot growth of atnigr1 (KO) and AtNIGR1 (OE) exhibited differential phenotypic responses under oxidative and nitro-oxidative stress and normal growth conditions. To investigate the role of the target gene in plant immunity, the biotrophic bacterial pathogen Pseudomonas syringae pv. tomato DC3000 virulent (Pst DC3000 vir) was used to assess the basal defense, while the Pst DC3000 avirulent (avrB) strain was used to investigate R-gene-mediated resistance and systemic acquired resistance (SAR). Data revealed that AtNIGR1 negatively regulated basal defense, R-gene-mediated resistance, and SAR. Furthermore, the Arabidopsis eFP browser indicated that the expression of AtNIGR1 is detected in several plant organs, with the highest expression observed in germinating seeds. All results put together suggest that AtNIGR1 could be involved in plant growth, as well as basal defense and SAR, in response to bacterial pathogens in Arabidopsis.
Keywords	Arabidopsis thaliana ; Pseudomonas syringae pv. tomato ; genes ; glutathione ; growth regulators ; hydrogen peroxide ; immunity ; nitric oxide ; paraquat ; pathogens ; phenotype ; plant growth ; systemic acquired resistance ; transcriptome ; virulence
Language	English
Dates of publication	2023-0424
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article ; Online
ZDB-ID	2704216-9
ISSN	2076-3921
ISSN	2076-3921
DOI	10.3390/antiox12050989
Database	NAL-Catalogue (AGRICOLA)

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