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1.
Curr Pharm Des ; 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38910414

RESUMO

BACKGROUND: Salivary Adenoid Cystic Carcinoma (ACC) is characterized by a highly invasive and slow-growing pattern, and its etiology remains unidentified. Triptonide (TN) has demonstrated efficacy as a pharmacotherapeutic agent against ACC. Nonetheless, the specific targets and mechanism of molecular action underlying the effectiveness of TN in treating ACC have not been elucidated. OBJECTIVES: By integrating network pharmacology with in-laboratory experiments, this research delves into the prospective targets and molecular mechanisms associated with the application of TN in treating ACC. METHODS: Initially, pertinent targets associated with TN against ACC were acquired from public databases. Subsequently, a combination of network pharmacology and bioinformatics analysis was utilized to screen the top 10 hub targets and key signal pathways of TN-treating ACC. Finally, in vitro experiments involving various molecular assays were conducted to evaluate the biological phenotypes of cells following TN treatment, encompassing assessments of apoptosis levels, plate migration, and other parameters, thereby validating pivotal genes and pathways. RESULTS: A total of 23 pertinent targets for TN in relation to ACC were identified, with the top 10 hub genes being MAPK8, PTGS2, RELA, MAPK14, NR3C1, HDAC1, PPARG, NFKBIA, AR, and PGR. There was a significant correlation between the TNF signaling pathway and the treatment of ACC with TN. In vitro experiments demonstrated that TN treatment elevated RELA phosphorylation while concurrently reducing MAPK14 phosphorylation and inducing G2/M arrest. TN exhibited the ability to enhance the apoptosis rate through increased caspase-3 activity, elevated levels of Reactive Oxygen Species (ROS), mitochondrial dysfunction, and inhibition of cell migration. CONCLUSION: There is a potential therapeutic role for TN in the treatment of ACC through the activation of the TNF signaling pathway. Among the identified candidates, MAPK8, HDAC1, PTGS2, RELA, NR3C1, PPARG, NFKBIA, AR, and PGR emerge as the most pertinent therapeutic targets for TN in the context of ACC treatment.

2.
Cell Death Dis ; 15(3): 178, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38429254

RESUMO

Tribbles pseudokinase 3 (TRIB3) has been identified recently as a novel oncogene in several cancers. Still, further extensive research is imperative to elucidate its function and the molecular mechanisms underlying its involvement in the progression of head and neck squamous cell carcinoma (HNSCC). In our study, we found that TRIB3 silencing significantly promoted cell death by inducing ferroptosis. The interaction of TRIB3 with Transcription Factor 4 (TCF4) and ß-catenin created a heterotrimeric complex, which directly interacts with the ALOXE3 promoter, detrimentally impacting its activation. The consequential partial neutralization of ferroptosis induced by TRIB3 deficiency is observed through the implementation of ALOXE3 knockdown. Furthermore, the study demonstrated that the molecular inhibitor hesperidin, targeting TRIB3, not only reduced cell malignancy but also induced ferroptosis, thereby suppressing tumor growth. Overall, our findings unequivocally validate the proposition that TRIB3 deficiency precipitates the iron death mechanism, thereby indicating that the strategic targeting of TRIB3 could emerge as an innovative therapeutic strategy for HNSCC.


Assuntos
Ferroptose , Neoplasias de Cabeça e Pescoço , Proteínas Serina-Treonina Quinases , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Proteínas de Ciclo Celular/metabolismo , Ferroptose/genética , Neoplasias de Cabeça e Pescoço/genética , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Repressoras/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética
3.
Photochem Photobiol ; 98(6): 1379-1389, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35538716

RESUMO

Ultraviolet (UV), particularly UVB, is widely used in the treatment of skin diseases including psoriasis, atopic dermatitis, vitiligo, mycosis fungoides and pruritus. Recently, there has been a trend of replacing broad-band UVB (BB-UVB) units with narrow-band UVB (NB-UVB), as studies have demonstrated that NB-UVB is more efficacious in the treatment of psoriasis. The purpose of this study is to evaluate the biological effects and transcriptome changes induced by light-emitting diode-based NB-UVB (NB-UVB LED) phototherapy. Cell viability and the cell migration ability were significantly decreased posttreatment, as well as apoptosis and ROS levels were remarkably increased. NB-UVB-induced S phase arrest was observed 12 h postirradiation. Bioinformatics analysis of transcriptome sequencing data revealed that NB-UVB LED irradiation induced dose-depended changes in multiple key signaling pathways, such as PI3K and cytoskeletal-related pathways. The depolymerization of cytoskeleton induced by NB-UVB was observed 24 h posttreatment. In addition, the expression levels of cytoskeleton-related proteins FN1, ITGB4, ITGA1, RAC2 and DOCK1 decreased significantly 12 h after irradiation. Our results indicated that NB-UVB LED may serve as a novel option for the development of NB-UVB phototherapy devices.


Assuntos
Psoríase , Terapia Ultravioleta , Vitiligo , Humanos , Transcriptoma , Resultado do Tratamento , Terapia Ultravioleta/métodos , Vitiligo/terapia , Psoríase/terapia , Fototerapia
4.
J Cancer ; 9(14): 2580-2588, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30026857

RESUMO

Cancer cells usually utilize glucose as a carbon source for aerobic glycolysis, a phenomenon known as the Warburg effect. And a high rate of glycolysis has been observed in lung cancer cells. The growing evidence indicates that long non-coding RNAs (lncRNAs) are important players in lung cancer initiation and progression. However, the correlation between lncRNAs and glycolysis remains unclear. In this study, we recognized a lncRNA, LNC CRYBG3, which can interact with lactate dehydrogenase A (LDHA), a vital enzyme of glycolysis, is highly upregulated in both clinical lung cancer tissues and in vitro cultured lung cancer cell lines. A positive correlation between the expression level of LNC CRYBG3 and LDHA expression levels is observed. In another hand, LNC CRYBG3 is a regulator of glycolysis and its overexpression promoted the uptake of glucose and the production of lactate whereas the knockdown of LNC CRYBG3 led to opposite results and suppressed cell proliferation. These results indicated that LNC CRYBG3 might be a novel target for lung cancer treatment.

5.
Cancer Res ; 78(16): 4563-4572, 2018 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-29934435

RESUMO

The dynamic interchange between monomeric globular actin (G-actin) and polymeric filamentous actin filaments (F-actin) is fundamental and essential to many cellular processes, including cytokinesis and maintenance of genomic stability. Here, we report that the long noncoding RNA LNC CRYBG3 directly binds G-actin to inhibit its polymerization and formation of contractile rings, resulting in M-phase cell arrest. Knockdown of LNC CRYBG3 in tumor cells enhanced their malignant phenotypes. Nucleotide sequence 228-237 of the full-length LNC CRYBG3 and the ser14 domain of ß-actin is essential for their interaction, and mutation of either of these sites abrogated binding of LNC CRYBG3 to G-actin. Binding of LNC CRYBG3 to G-actin blocked nuclear localization of MAL, which consequently kept serum response factor (SRF) away from the promoter region of several immediate early genes, including JUNB and Arp3, which are necessary for cellular proliferation, tumor growth, adhesion, movement, and metastasis. These findings reveal a novel lncRNA-actin-MAL-SRF pathway and highlight LNC CRYBG3 as a means to block cytokinesis and to treat cancer by targeting the actin cytoskeleton.Significance: Identification of the long noncoding RNA LNC CRYBG3 as a mediator of microfilament disorganization marks it as a novel therapeutic antitumor strategy. Cancer Res; 78(16); 4563-72. ©2018 AACR.


Assuntos
Actinas/genética , Proliferação de Células/genética , Citocinese/genética , RNA Longo não Codificante/genética , Pontos de Checagem do Ciclo Celular/genética , Movimento Celular/genética , Núcleo Celular/genética , Humanos , Transdução de Sinais , Cadeia B de beta-Cristalina/genética
6.
Zhongguo Zhong Yao Za Zhi ; 42(20): 3938-3944, 2017 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-29243431

RESUMO

To study sesquiterpenes with anti-metastasis breast cancer activity from Chloranthus henryi, ten sesquiterpenes ,zedoarofuran (1), chlorajapolide D (2), 4ß, 8ß-dihydroxy-5α(H)-eudesm-7(11)-en-8, 12-olide (3), curcolonol (4), lasianthuslactone A (5), chlomultin C (6), (1E,4Z)-8-hydroxy-6-oxogermacra-1(10), 4, 7(11) -trieno-12, 8-lactone (7), shizukanolide E (8) , shizukanolide F (9) , 9α-hydroxycurcolonol (10), and five bis-sesquiterpenes, shizukaol B (11), shizukaol C (12) , cycloshizukaol A (13) , sarcandrolide B (14) , henriol A(15), were isolated by using different kinds of column chromatography methods from the ethyl acetate part of Ch.henryi and their structures were identified based on spectroscopic methods. Compounds 2, 8, 9, and 10 were obtained from the genus Chloranthus for the first time. Compounds 2, 5, 8-10, 12,and 14 were obtained from this plant for the first time. Some isolated compounds were subjected to evaluate the anti-metastasis breast cancer activity by using pharmacological methods, and only compounds 4, 11, and 12 were potent active.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Neoplasias da Mama/patologia , Sesquiterpenos/farmacologia , Traqueófitas/química , Antineoplásicos Fitogênicos/isolamento & purificação , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Humanos , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Sesquiterpenos/isolamento & purificação
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