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Article ; Online: Arenobufagin induces cell apoptosis by modulating the cell cycle regulator claspin and the JNK pathway in nasopharyngeal carcinoma cells.

Ho, Hsin-Yu / Chen, Mu-Kuan / Lin, Chia-Chieh / Lo, Yu-Sheng / Chuang, Yi-Ching / Hsieh, Ming-Ju

2024 , Page(s) 1–11

Abstract: Background: The high recurrence rate and incidence of distant metastasis of nasopharyngeal carcinoma (NPC) result in poor prognosis. It is necessary to identify natural compounds that can complement combination radiation therapy. Arenobufagin is ... ...

Abstract	Background: The high recurrence rate and incidence of distant metastasis of nasopharyngeal carcinoma (NPC) result in poor prognosis. It is necessary to identify natural compounds that can complement combination radiation therapy. Arenobufagin is commonly used for heart diseases and liver cancer, but its effectiveness in NPC is unclear. Study design and methods: The effect of arenobufagin-induced apoptosis was measured by a cell viability assay, tumorigenic assay, fluorescence assay, and Western blot assay through NPC-039 and NPC-BM cell lines. The protease array, Western blot assay, and transient transfection were used to investigate the underlying mechanism of arenobufagin-induced apoptosis. An NPC xenograft model was established to explore the antitumor activity of arenobufagin Results: Our findings indicated that arenobufagin exerted cytotoxic effects on NPC cells, inhibiting proliferation through apoptosis activation. Downregulation of claspin was confirmed in arenobufagin-induced apoptosis. Combined treatment with arenobufagin and mitogen-activated protein kinase inhibitors demonstrated that arenobufagin induced NPC apoptosis through the c-Jun N-terminal kinases (JNK) pathway inhibition. Furthermore, arenobufagin suppressed NPC tumor proliferation in vivo. Conclusion: Our results revealed the antitumor effect of arenobufagin in vitro and in vivo. Arenobufagin may have clinical utility in treating NPC due to its suppression of claspin and inhibition of the JNK pathway.
Language	English
Publishing date	2024-04-27
Publishing country	England
Document type	Journal Article
ZDB-ID	2055208-7
ISSN	1744-7631 ; 1472-8222
ISSN (online)	1744-7631
ISSN	1472-8222
DOI	10.1080/14728222.2024.2348014
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Article ; Online: The Interaction between CLSPN Gene Polymorphisms and Alcohol Consumption Contributes to Oral Cancer Progression.

Hsieh, Ming-Ju / Lo, Yu-Sheng / Ho, Hsin-Yu / Lin, Chia-Chieh / Chuang, Yi-Ching / Chen, Mu-Kuan

International journal of molecular sciences

2024 Volume 25, Issue 2

Abstract: Most disease single nucleotide polymorphisms (SNPs) are regulatory and approximately half of heritability is occupied by the top 1% of genes, with the gene-level structure varying with the number of variants associated with the most common alleles. ... ...

Abstract	Most disease single nucleotide polymorphisms (SNPs) are regulatory and approximately half of heritability is occupied by the top 1% of genes, with the gene-level structure varying with the number of variants associated with the most common alleles. Cancer occurrence and progression are significantly affected by Claspin (CLSPN) gene polymorphism present in the population, which alters the expression, function, and regulation of the gene. CLSPN genotypes are associated with oral cancer, but the literature on this association is limited. As a result, the goal of this study is to investigate the correlation between CLSPN genotypes and oral cancers' development. This study will explore the presence of four CLSPN SNPs including rs12058760, rs16822339, rs535638 and rs7520495 gene polymorphisms, and analyze the expression of these genes in 304 cancer-free controls and 402 oral squamous cell carcinoma (OSCC) cases. Attempts have been made to obtain insight into the role of CLSPN gene polymorphisms in oral cancer through the analysis of this study. We demonstrated that the OSCC risk of individuals with four CLSPN SNPs relative to the wild type did not differ significantly from that of the wild type when the polymorphisms are analyzed according to individual habits. We further studied the mechanism by which CLSPN polymorphisms affect the progression of clinicopathological features in OSCC patients. The results of the degree of cell differentiation showed that compared with patients of rs7520495 SNP carrying the CC genotype, the incidence of poor cell differentiation in patients carrying the CC + GG genotype was higher (AOR: 1.998-fold; 95% CI, 1.127-3.545; p = 0.018). In particular, patients with the G genotype of rs7520495 had increased poor cell differentiation compared with patients with the C genotype (AOR: 4.736-fold; 95% CI, 1.306-17.178; p = 0.018), especially in the drinking group. On the basis of our analysis of the Cancer Genome Atlas dataset, we found that higher CLSPN levels were associated with poorer cell differentiation in oral cancers. In this study, we provide the first evidence showing that CLSPN SNPs contribute to oral cancer. Whether or not rs7520495 can be used as a confirmatory factor in the future is uncertain, but it seems likely that it can be used as an important factor in predicting recurrence, response to treatment and medication toxicity to patients with oral cancer.
MeSH term(s)	Humans ; Adaptor Proteins, Signal Transducing/genetics ; Alcohol Drinking/genetics ; Mouth Neoplasms/genetics ; Polymorphism, Single Nucleotide ; Squamous Cell Carcinoma of Head and Neck/genetics
Chemical Substances	Adaptor Proteins, Signal Transducing ; CLSPN protein, human
Language	English
Publishing date	2024-01-16
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/ijms25021098
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Article ; Online: LDL Receptor-Related Protein 1B Polymorphisms Associated with Increased Risk of Lymph Node Metastasis in Oral Cancer Group with Diabetes Mellitus.

Chen, Liang-Cheng / Lo, Yu-Sheng / Ho, Hsin-Yu / Lin, Chia-Chieh / Chuang, Yi-Ching / Chang, Wei-Chen / Hsieh, Ming-Ju

International journal of molecular sciences

2024 Volume 25, Issue 7

Abstract: Oral cancer ranks fourth among malignancies among Taiwanese men and is the eighth most common cancer among men worldwide in terms of general diagnosis. The purpose of the current study was to investigate how low-density lipoprotein receptor-related ... ...

Abstract	Oral cancer ranks fourth among malignancies among Taiwanese men and is the eighth most common cancer among men worldwide in terms of general diagnosis. The purpose of the current study was to investigate how low-density lipoprotein receptor-related protein 1B (LDL receptor related protein 1B; LRP1B) gene polymorphisms affect oral squamous cell carcinoma (OSCC) risk and progression in individuals with diabetes mellitus (DM). Three LRP1B single-nucleotide polymorphisms (SNPs), including rs10496915, rs431809, and rs6742944, were evaluated in 311 OSCC cases and 300 controls. Between the case and control groups, we found no evidence of a significant correlation between the risk of OSCC and any of the three specific SNPs. Nevertheless, in evaluating the clinicopathological criteria, individuals with DM who possess a minimum of one minor allele of rs10496915 (AC + CC;
MeSH term(s)	Male ; Humans ; Mouth Neoplasms/genetics ; Lymphatic Metastasis ; Carcinoma, Squamous Cell/genetics ; Polymorphism, Single Nucleotide ; Diabetes Mellitus ; Squamous Cell Carcinoma of Head and Neck ; Head and Neck Neoplasms ; Receptors, LDL/genetics
Chemical Substances	Receptors, LDL
Language	English
Publishing date	2024-04-02
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/ijms25073963
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Article ; Online: Semilicoisoflavone B induces oral cancer cell apoptosis by targeting claspin and ATR-Chk1 signaling pathways.

Hsieh, Ming-Ju / Lin, Chia-Chieh / Lo, Yu-Sheng / Chuang, Yi-Ching / Ho, Hsin-Yu / Chen, Mu-Kuan

Environmental toxicology

2024 Volume 39, Issue 4, Page(s) 2417–2428

Abstract: The prevalence of oral squamous cell carcinoma (OSCC) is increasing worldwide mainly due to poor oral hygiene and unrestricted lifestyle. Advanced-stage OSCC is associated with poor prognosis and a 5-year survival rate of only 30%-50%. The present study ... ...

Abstract	The prevalence of oral squamous cell carcinoma (OSCC) is increasing worldwide mainly due to poor oral hygiene and unrestricted lifestyle. Advanced-stage OSCC is associated with poor prognosis and a 5-year survival rate of only 30%-50%. The present study was designed to investigate the anticancer effect and mode of action of Glycyrrhiza-derived semilicoisoflavone B (SFB) in 5-fluorourasil (5FU)-resistant human OSCC cell lines. The study findings revealed that SFB significantly reduces OSCC cell viability and colony formation ability by arresting cell cycle at the G2/M and S phases and reducing the expressions of key cell cycle regulators including cyclin A, cyclin B, CDC2, and CDK2. The compound caused a significant induction in the percentage of nuclear condensation and apoptotic cells in OSCC. Regarding pro-apoptotic mode of action, SFB was found to increase Fas-associated death domain and death receptor 5 expressions and reduce decoy receptor 2 expression, indicating involvement of extrinsic pathway. Moreover, SFB was found to increase pro-apoptotic Bim expression and reduce anti-apoptotic Bcl-2 and Bcl-xL expressions, indicating involvement of intrinsic pathway. Moreover, SFB-mediated induction in cleaved caspases 3, 8, and 9 and cleaved poly(ADP-ribose) polymerase confirmed the induction of caspase-mediated apoptotic pathways. Regarding upstream signaling pathway, SFB was found to reduce extracellular signal regulated kinase 1/2 (ERK) phosphorylation to execute its pro-apoptotic activity. The Human Apoptotic Array findings revealed that SFB suppresses claspin expression, which in turn caused reduced phosphorylation of ATR, checkpoint kinase 1 (Chk1), Wee1, and CDC25C, indicating disruption of ATR-Chk1 signaling pathway by SFB. Taken together, these findings indicate that SFB acts as a potent anticancer compound against 5FU-resistant OSCC by modulating mitogen-activated protein kinase (MAPK) and ATR-Chk1 signaling pathways.
MeSH term(s)	Humans ; Checkpoint Kinase 1 ; Carcinoma, Squamous Cell ; Mouth Neoplasms ; Apoptosis ; Signal Transduction ; Phosphorylation ; Fluorouracil ; Cell Line, Tumor ; Ataxia Telangiectasia Mutated Proteins ; Flavonoids
Chemical Substances	semilicoisoflavone B (T9TP371NFX) ; Checkpoint Kinase 1 (EC 2.7.11.1) ; Fluorouracil (U3P01618RT) ; ATR protein, human (EC 2.7.11.1) ; Ataxia Telangiectasia Mutated Proteins (EC 2.7.11.1) ; Flavonoids
Language	English
Publishing date	2024-01-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	1463449-1
ISSN	1522-7278 ; 1520-4081
ISSN (online)	1522-7278
ISSN	1520-4081
DOI	10.1002/tox.24107
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Article ; Online: FAM13A polymorphisms are associated with a specific susceptibility to clinical progression of oral cancer in alcohol drinkers.

Hsieh, Ming-Ju / Lo, Yu-Sheng / Tsai, Yun-Jung / Ho, Hsin-Yu / Lin, Chia-Chieh / Chuang, Yi-Ching / Lin, Shu-Hui / Chen, Mu-Kuan

BMC cancer

2023 Volume 23, Issue 1, Page(s) 607

Abstract: Background: Single nucleotide polymorphism (SNP) is a genetic variation that occurs when a single nucleotide base in the DNA sequence varies between individuals and is present in at least 1% of the population. Genetic variants in FAM13A are associated ... ...

Abstract	Background: Single nucleotide polymorphism (SNP) is a genetic variation that occurs when a single nucleotide base in the DNA sequence varies between individuals and is present in at least 1% of the population. Genetic variants in FAM13A are associated with different types of chronic respiratory diseases, including chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), and lung cancer. However, there is little literature on the association of FAM13A genotypes with oral cancer. Therefore, this project will explore the correlation between the FAM13A genotype and the formation of oral cancer. Methods: In this project, we will examine the presence of gene polymorphisms gene polymorphisms of rs1059122, rs3017895, rs3756050, and rs7657817 in the FAM13A gene exon, and combine the expression of these genes to try to clarify the impact of the FAM13A gene polymorphism on oral cancer. First, four loci (rs1059122, rs3017895, rs3756050, and rs7657817) of the FAM13A SNP were genotyped using TaqMan allelic discrimination. Results: By estimating OR and AOR, FAM13A exhibited different genotypic variables in four SNPs that were not statistically significant between controls and patients with oral cancer. The results of the general analysis showed that different distributions of allelic types did not affect clinical stage, tumour size, lymph node invasion, distant metastasis, and pathological differentiation status. However, in the alcohol drinking group specifically, patients with the rs3017895 SNP G genotype had a 3.17-fold (95% CI, 1.102-9.116; p = 0.032) increase in the well differentiated state of cells compared to patients with the A allele. Conclusions: Our results suggested that the SNP rs3017895 FAM13A could contribute to oral cancer. More sample studies are needed in the future to confirm our results and more functional studies are needed to investigate their relevant roles in the development of oral cancer.
MeSH term(s)	Humans ; Disease Progression ; Genes, Regulator ; GTPase-Activating Proteins/genetics ; Mouth Neoplasms/genetics ; Polymorphism, Single Nucleotide ; Alcohol Drinking/adverse effects
Chemical Substances	FAM13A protein, human ; GTPase-Activating Proteins
Language	English
Publishing date	2023-06-30
Publishing country	England
Document type	Journal Article
ZDB-ID	2041352-X
ISSN	1471-2407 ; 1471-2407
ISSN (online)	1471-2407
ISSN	1471-2407
DOI	10.1186/s12885-023-11052-5
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Article ; Online: Semilicoisoflavone B Induces Apoptosis of Oral Cancer Cells by Inducing ROS Production and Downregulating MAPK and Ras/Raf/MEK Signaling.

Hsieh, Ming-Ju / Ho, Hsin-Yu / Lo, Yu-Sheng / Lin, Chia-Chieh / Chuang, Yi-Ching / Abomughaid, Mosleh Mohammad / Hsieh, Ming-Chang / Chen, Mu-Kuan

International journal of molecular sciences

2023 Volume 24, Issue 5

Abstract: Oral squamous cell carcinoma (OSCC) is the sixth most common type of cancer worldwide. Despite advancement in treatment, advanced-stage OSCC is associated with poor prognosis and high mortality. The present study aimed to investigate the anticancer ... ...

Abstract	Oral squamous cell carcinoma (OSCC) is the sixth most common type of cancer worldwide. Despite advancement in treatment, advanced-stage OSCC is associated with poor prognosis and high mortality. The present study aimed to investigate the anticancer activities of semilicoisoflavone B (SFB), which is a natural phenolic compound isolated from
MeSH term(s)	Humans ; Apoptosis/drug effects ; Carcinoma, Squamous Cell/drug therapy ; Carcinoma, Squamous Cell/metabolism ; Cell Line, Tumor ; Cell Proliferation ; Mitogen-Activated Protein Kinase Kinases ; Mouth Neoplasms/drug therapy ; Mouth Neoplasms/metabolism ; Reactive Oxygen Species/metabolism ; Mitogen-Activated Protein Kinases/drug effects ; Mitogen-Activated Protein Kinases/metabolism ; ras Proteins/drug effects ; ras Proteins/metabolism ; Proto-Oncogene Proteins c-raf/drug effects ; Proto-Oncogene Proteins c-raf/metabolism
Chemical Substances	Mitogen-Activated Protein Kinase Kinases (EC 2.7.12.2) ; Reactive Oxygen Species ; semilicoisoflavone B (T9TP371NFX) ; Mitogen-Activated Protein Kinases (EC 2.7.11.24) ; ras Proteins (EC 3.6.5.2) ; Proto-Oncogene Proteins c-raf (EC 2.7.11.1)
Language	English
Publishing date	2023-02-24
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/ijms24054505
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Article ; Online: Picrasidine J, a Dimeric β-Carboline-Type Alkaloid from

Ho, Hsin-Yu / Lin, Chia-Chieh / Lo, Yu-Sheng / Chuang, Yi-Ching / Abomughaid, Mosleh Mohammad / Hsieh, Ming-Ju

International journal of molecular sciences

2023 Volume 24, Issue 17

Abstract: Head and neck squamous cell carcinoma (HNSCC) are associated with recurrence, distant metastasis, and poor overall survival. This highlights the need for identifying potential therapeutics with minimal side-effects. The present study was designed to ... ...

Abstract	Head and neck squamous cell carcinoma (HNSCC) are associated with recurrence, distant metastasis, and poor overall survival. This highlights the need for identifying potential therapeutics with minimal side-effects. The present study was designed to investigate the anticancer effects of picrasidine J, a dimeric β-carboline-type alkaloid isolated from the southern Asian plant
MeSH term(s)	Picrasma ; Squamous Cell Carcinoma of Head and Neck ; Alkaloids/pharmacology ; Carbolines ; Antineoplastic Agents/pharmacology ; Polymers ; Head and Neck Neoplasms/drug therapy
Chemical Substances	Alkaloids ; Carbolines ; Antineoplastic Agents ; Polymers
Language	English
Publishing date	2023-08-25
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/ijms241713230
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Article ; Online: Hellebrigenin induces oral cancer cell apoptosis by modulating MAPK signalling and XIAP expression.

Hsieh, Ming-Ju / Lin, Chia-Chieh / Lo, Yu-Sheng / Ho, Hsin-Yu / Chuang, Yi-Ching / Chen, Mu-Kuan

Journal of cellular and molecular medicine

2023 Volume 28, Issue 2, Page(s) e18071

Abstract: Oral squamous cell carcinoma (OSCC), which accounts for 90% of all oral cancers, has become a public health crisis worldwide. despite advances in therapeutic interventions, the prognosis remains poor for advanced-stage OSCC. In this study, we investigate ...

Abstract	Oral squamous cell carcinoma (OSCC), which accounts for 90% of all oral cancers, has become a public health crisis worldwide. despite advances in therapeutic interventions, the prognosis remains poor for advanced-stage OSCC. In this study, we investigate the anticancer activity and the mode of action of hellebrigenin in human OSCC. The findings demonstrated that hellebrigenin exerted cytotoxic effects in OSCC cells through cell cycle arrest at the G2/M phase and downregulation of cell cycle-related proteins (cyclins A2, B1 and D3, Cdc2, CDK4 and CDK6). Moreover, hellebrigenin caused activation of PARP and caspase 3, 8 and 9, followed by downregulation of antiapoptotic proteins (Bcl-2 and Bcl-xL) and upregulation of pro-apoptotic proteins (Bax and Bak). The hellebrigenin treatment also increased Fas, DR5, DcR2 and DcR3 expressions in oral cancer cells, indicating the compound causes oral cancer cell apoptosis through both intrinsic and extrinsic pathways. Regarding upstream signalling, hellebrigenin was found to reduce the phosphorylation of ERK, p38, and JNK, indicating that hellebrigenin triggers caspase-mediated apoptosis by downregulating MAPK signalling pathway. Finally, the human apoptosis array findings revealed that hellebrigenin specifically suppressed the expression of XIAP to execute its pro-apoptotic activities. Taken together, the study suggests that hellebrigenin can act as a potent anticancer compound in human OSCC.
MeSH term(s)	Humans ; Mouth Neoplasms/drug therapy ; Mouth Neoplasms/genetics ; Mouth Neoplasms/pathology ; Carcinoma, Squamous Cell/drug therapy ; Carcinoma, Squamous Cell/genetics ; Carcinoma, Squamous Cell/metabolism ; Signal Transduction ; Apoptosis/physiology ; Cell Cycle Proteins/metabolism ; Cell Line, Tumor ; Cell Proliferation ; X-Linked Inhibitor of Apoptosis Protein/genetics ; X-Linked Inhibitor of Apoptosis Protein/metabolism ; Bufanolides
Chemical Substances	hellebrigenin (465-90-7) ; Cell Cycle Proteins ; XIAP protein, human ; X-Linked Inhibitor of Apoptosis Protein ; Bufanolides
Language	English
Publishing date	2023-12-03
Publishing country	England
Document type	Journal Article
ZDB-ID	2074559-X
ISSN	1582-4934 ; 1582-4934 ; 1582-1838
ISSN (online)	1582-4934
ISSN	1582-4934 ; 1582-1838
DOI	10.1111/jcmm.18071
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Article ; Online: Epiberberine suppresses the metastasis of head and neck squamous cell carcinoma cells by regulating the MMP-13 and JNK pathway.

Ho, Hsin-Yu / Chen, Mu-Kuan / Lin, Chia-Chieh / Lo, Yu-Sheng / Chuang, Yi-Ching / Hsieh, Ming-Ju

Journal of cellular and molecular medicine

2023 Volume 27, Issue 23, Page(s) 3796–3804

Abstract: Head and neck squamous cell carcinoma (HNSCC) is one of the most common histological types of head and neck cancer. Epiberberine is a potent antitumour agent for several types of cancer. This study is aimed at investigating the regulatory and molecular ... ...

Abstract	Head and neck squamous cell carcinoma (HNSCC) is one of the most common histological types of head and neck cancer. Epiberberine is a potent antitumour agent for several types of cancer. This study is aimed at investigating the regulatory and molecular mechanism of epiberberine on HNSSC cell metastasis. The results showed that epiberberine inhibited the motility of Ca9-22 and FaDu cell lines at nontoxicity doses. Moreover, the epithelial-mesenchymal transition (EMT)-related proteins, vimentin, snail and slug, were found suppressing after epiberberine treatments. In addition, the JNK signalling cascade and the metalloproteinase 13 (MMP-13) expression were also found downregulated by epiberberine. In conclusion, the present study demonstrates that epiberberine suppresses cell migration and invasion by regulating the JNK pathway and MMP-13. These results suggest that epiberberine could be a potential antimetastatic agent in HNSCC cells.
MeSH term(s)	Humans ; Squamous Cell Carcinoma of Head and Neck/drug therapy ; Matrix Metalloproteinase 13/genetics ; Matrix Metalloproteinase 13/metabolism ; Carcinoma, Squamous Cell/genetics ; MAP Kinase Signaling System ; Cell Line, Tumor ; Head and Neck Neoplasms/drug therapy ; Antineoplastic Agents/pharmacology ; Epithelial-Mesenchymal Transition ; Neoplasm Invasiveness ; Cell Movement ; Gene Expression Regulation, Neoplastic
Chemical Substances	Matrix Metalloproteinase 13 (EC 3.4.24.-) ; epiberberine (6873-09-2) ; Antineoplastic Agents
Language	English
Publishing date	2023-09-14
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2074559-X
ISSN	1582-4934 ; 1582-4934 ; 1582-1838
ISSN (online)	1582-4934
ISSN	1582-4934 ; 1582-1838
DOI	10.1111/jcmm.17954
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Article ; Online: Limocitrin increases cytotoxicity of KHYG-1 cells against K562 cells by modulating MAPK pathway.

Hsieh, Ming-Ju / Lin, Jen-Tsun / Chuang, Yi-Ching / Lin, Chia-Chieh / Lo, Yu-Sheng / Ho, Hsin-Yu / Chen, Mu-Kuan

Environmental toxicology

2023 Volume 38, Issue 12, Page(s) 2939–2951

Abstract: Natural killer (NK) cells are gaining popularity in the field of cancer immunotherapy. The present study was designed to investigate the effect of a natural flavonol compound limocitrin in increasing cytotoxicity of a permanent NK leukemia cell line KHYG- ...

Abstract	Natural killer (NK) cells are gaining popularity in the field of cancer immunotherapy. The present study was designed to investigate the effect of a natural flavonol compound limocitrin in increasing cytotoxicity of a permanent NK leukemia cell line KHYG-1 against an aggressive leukemia cell line K562. The findings revealed that limocitrin increased the expressions of cytolytic molecules perforin, granzymes A and B, and granulysin in KHYG-1 cells by inducing phosphorylation of transcription factor CREB, leading to increased lysis of K562 cells. Mechanistically, limocitrin was found to increase the expressions of t-Bid, cleaved caspase 3, and cleaved PARP to induce K562 cell apoptosis. Moreover, limocitrin reduced the expressions of SET and Ape1 to inhibit DNA repair mechanism, leading to caspase-independent K562 cell death. At the molecular level, limocitrin was found to increase the phosphorylation of ERK, p38, and JNK to increase granzyme B expression in KHYG-1 cells. Taken together, the study indicates that limocitrin increases cytotoxicity of NK cells against a range of cancer cells.
MeSH term(s)	Humans ; K562 Cells ; Killer Cells, Natural ; Perforin/metabolism ; Leukemia ; Cytotoxicity, Immunologic
Chemical Substances	Perforin (126465-35-8)
Language	English
Publishing date	2023-08-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	1463449-1
ISSN	1522-7278 ; 1520-4081
ISSN (online)	1522-7278
ISSN	1520-4081
DOI	10.1002/tox.23929
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