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1.
Med Oncol ; 41(7): 167, 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38831079

RESUMEN

Cancer stem cells (CSCs) are mainly responsible for tumorigenesis, chemoresistance, and cancer recurrence. CSCs growth and progression are regulated by multiple signaling cascades including Wnt/ß-catenin and Hh/GLI-1, which acts independently or via crosstalk. Targeting the crosstalk of signaling pathways would be an effective approach to control the CSC population. Both Wnt/ß-catenin and Hh/GLI-1 signaling cascades are known to be regulated by p53/p21-dependent mechanism. However, it is interesting to delineate whether p21 can induce apoptosis in a p53-independent manner. Therefore, utilizing various subtypes of oral CSCs (SCC9-PEMT p53+/+p21+/+, SCC9-PEMT p53-/-p21+/+, SCC9-PEMT p53+/+p21-/- and SCC9-PEMT p53-/-p21-/-), we have examined the distinct roles of p53 and p21 in Resveratrol nanoparticle (Res-Nano)-mediated apoptosis. It is interesting to see that, besides the p53/p21-mediated mechanism, Res-Nano exposure also significantly induced apoptosis in oral CSCs through a p53-independent activation of p21. Additionally, Res-Nano-induced p21-activation deregulated the ß-catenin-GLI-1 complex and consequently reduced the TCF/LEF and GLI-1 reporter activities. In agreement with in vitro data, similar experimental results were obtained in in vivo mice xenograft model.


Asunto(s)
Apoptosis , Inhibidor p21 de las Quinasas Dependientes de la Ciclina , Neoplasias de la Boca , Nanopartículas , Células Madre Neoplásicas , Resveratrol , Proteína p53 Supresora de Tumor , Proteína con Dedos de Zinc GLI1 , beta Catenina , Apoptosis/efectos de los fármacos , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Resveratrol/farmacología , Proteína con Dedos de Zinc GLI1/metabolismo , Proteína con Dedos de Zinc GLI1/genética , beta Catenina/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Humanos , Neoplasias de la Boca/patología , Neoplasias de la Boca/tratamiento farmacológico , Neoplasias de la Boca/metabolismo , Animales , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Ratones , Línea Celular Tumoral , Ensayos Antitumor por Modelo de Xenoinjerto
2.
Mol Biol Rep ; 51(1): 723, 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38833199

RESUMEN

BACKGROUND: Glioblastoma multiforme, a deadly form of brain tumor, is characterized by aggressive growth and poor prognosis. Oxidative stress, a disruption in the balance between antioxidants and oxidants, is a crucial factor in its pathogenesis. Silymarin, a flavonoid extracted from milk thistle, has shown therapeutic potential in inhibiting cancer cell growth, promoting apoptosis, and reducing inflammation. It also regulates oxidative stress. This study aims to investigate the regulatory effects of silymarin on oxidative stress parameters, especially the transcription factor Nrf2 and its related enzymes in GBM cancer cells, to develop a new anti-cancer compound with low toxicity. METHODS AND RESULTS: First, the cytotoxicity of silymarin on U-87 MG cells was investigated by MTT and the results showed an IC50 of 264.6 µM. Then, some parameters of the redox system were measured with commercial kits, and the obtained results showed that silymarin increased the activity of catalase and superoxide dismutase enzymes, as well as the total antioxidant capacity levels; while the malondialdehyde level that is an indicator of lipid peroxidation was decreased by this compound. The expression level of Nrf2 and HO-1 and glutaredoxin and thioredoxin enzymes were checked by real-time PCR method, and the expression level increased significantly after treatment. CONCLUSIONS: Our findings suggest that silymarin may exert its cytotoxic and anticancer effects by enhancing the Nrf2/HO-1 pathway through antioxidant mechanisms in U-87 MG cells.


Asunto(s)
Antioxidantes , Glioblastoma , Factor 2 Relacionado con NF-E2 , Oxidación-Reducción , Estrés Oxidativo , Silimarina , Silimarina/farmacología , Humanos , Glioblastoma/tratamiento farmacológico , Glioblastoma/metabolismo , Glioblastoma/patología , Línea Celular Tumoral , Oxidación-Reducción/efectos de los fármacos , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo/efectos de los fármacos , Antioxidantes/farmacología , Superóxido Dismutasa/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Apoptosis/efectos de los fármacos , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Catalasa/metabolismo , Catalasa/genética
3.
Mol Biol Rep ; 51(1): 701, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38822973

RESUMEN

BACKGROUND: Disabled 2 (DAB2) is a multifunctional protein that has emerged as a critical component in the regulation of tumor growth. Its dysregulation is implicated in various types of cancer, underscoring its importance in understanding the molecular mechanisms underlying tumor development and progression. This review aims to unravel the intricate molecular mechanisms by which DAB2 exerts its tumor-suppressive functions within cancer signaling pathways. METHODS AND RESULTS: We conducted a comprehensive review of the literature focusing on the structure, expression, physiological functions, and tumor-suppressive roles of DAB2. We provide an overview of the structure, expression, and physiological functions of DAB2. Evidence supporting DAB2's role as a tumor suppressor is explored, highlighting its ability to inhibit cell proliferation, induce apoptosis, and modulate key signaling pathways involved in tumor suppression. The interaction between DAB2 and key oncogenes is examined, elucidating the interplay between DAB2 and oncogenic signaling pathways. We discuss the molecular mechanisms underlying DAB2-mediated tumor suppression, including its involvement in DNA damage response and repair, regulation of cell cycle progression and senescence, and modulation of epithelial-mesenchymal transition (EMT). The review explores the regulatory networks involving DAB2, covering post-translational modifications, interactions with other tumor suppressors, and integration within complex signaling networks. We also highlight the prognostic significance of DAB2 and its role in pre-clinical studies of tumor suppression. CONCLUSION: This review provides a comprehensive understanding of the molecular mechanisms by which DAB2 exerts its tumor-suppressive functions. It emphasizes the significance of DAB2 in cancer signaling pathways and its potential as a target for future therapeutic interventions.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales , Proteínas Reguladoras de la Apoptosis , Neoplasias , Transducción de Señal , Humanos , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patología , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Proteínas Reguladoras de la Apoptosis/genética , Animales , Transición Epitelial-Mesenquimal/genética , Progresión de la Enfermedad , Proteínas Supresoras de Tumor/metabolismo , Proteínas Supresoras de Tumor/genética , Regulación Neoplásica de la Expresión Génica , Proliferación Celular/genética , Carcinogénesis/genética , Carcinogénesis/metabolismo , Apoptosis/genética
4.
Reprod Domest Anim ; 59(6): e14628, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38828525

RESUMEN

This study aimed to investigate the impact of the epidermal growth factor receptor ligands amphiregulin (AREG) and epiregulin (EREG) on the fundamental functions of feline ovarian granulosa cells. Granulosa cells isolated from feline ovaries were incubated with AREG and EREG (0, 0.1, 1 or 10 ng/mL). The effects of these growth factors on cell viability, proliferation (assessed through BrdU incorporation), nuclear apoptosis (evaluated through nuclear DNA fragmentation) and the release of progesterone and estradiol were determined using Cell Counting Kit-8 assays, BrdU analysis, TUNEL assays and ELISAs, respectively. Both AREG and EREG increased cell viability, proliferation and steroid hormone release and reduced apoptosis. The present findings suggest that these epidermal growth factor receptor ligands may serve as physiological stimulators of feline ovarian cell functions.


Asunto(s)
Anfirregulina , Apoptosis , Proliferación Celular , Supervivencia Celular , Epirregulina , Células de la Granulosa , Animales , Gatos , Femenino , Células de la Granulosa/efectos de los fármacos , Células de la Granulosa/metabolismo , Anfirregulina/metabolismo , Anfirregulina/genética , Epirregulina/metabolismo , Epirregulina/genética , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Progesterona/metabolismo , Progesterona/farmacología , Estradiol/metabolismo , Estradiol/farmacología , Células Cultivadas
5.
J Nanobiotechnology ; 22(1): 303, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38822376

RESUMEN

Radiation-induced intestinal injury is the most common side effect during radiotherapy of abdominal or pelvic solid tumors, significantly impacting patients' quality of life and even resulting in poor prognosis. Until now, oral application of conventional formulations for intestinal radioprotection remains challenging with no preferred method available to mitigate radiation toxicity in small intestine. Our previous study revealed that nanomaterials derived from spore coat of probiotics exhibit superior anti-inflammatory effect and even prevent the progression of cancer. The aim of this work is to determine the radioprotective effect of spore coat (denoted as spore ghosts, SGs) from three clinically approved probiotics (B.coagulans, B.subtilis and B.licheniformis). All the three SGs exhibit outstanding reactive oxygen species (ROS) scavenging ability and excellent anti-inflammatory effect. Moreover, these SGs can reverse the balance of intestinal flora by inhibiting harmful bacteria and increasing the abundance of Lactobacillus. Consequently, administration of SGs significantly reduce radiation-induced intestinal injury by alleviating diarrhea, preventing X-ray induced apoptosis of small intestinal epithelial cells and promoting restoration of barrier integrity in a prophylactic study. Notably, SGs markedly improve weight gain and survival of mice received total abdominal X-ray radiation. This work may provide promising radioprotectants for efficiently attenuating radiation-induced gastrointestinal syndrome and promote the development of new intestinal predilection.


Asunto(s)
Probióticos , Protectores contra Radiación , Esporas Bacterianas , Animales , Probióticos/farmacología , Ratones , Administración Oral , Protectores contra Radiación/farmacología , Protectores contra Radiación/uso terapéutico , Protectores contra Radiación/química , Esporas Bacterianas/efectos de la radiación , Traumatismos por Radiación/tratamiento farmacológico , Especies Reactivas de Oxígeno/metabolismo , Intestino Delgado/microbiología , Intestino Delgado/efectos de la radiación , Intestino Delgado/patología , Humanos , Apoptosis/efectos de los fármacos , Masculino , Microbioma Gastrointestinal/efectos de los fármacos , Intestinos/efectos de la radiación , Intestinos/microbiología , Intestinos/patología , Traumatismos Experimentales por Radiación/patología
6.
Immun Inflamm Dis ; 12(6): e1169, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38860757

RESUMEN

INTRODUCTION: We aimed to explore the molecular mechanisms through which platelet-rich plasma (PRP) attenuates osteoarthritis (OA)-induced pain, apoptosis, and inflammation. METHODS: An in vivo model of OA was established by injuring rats using the anterior cruciate ligament transection method, whereas an in vitro model was generated by exposing chondrocytes to interleukin (IL)-1ß. Both models were then treated with PRP. RESULTS: In both the in vivo and in vitro models, OA led to the suppression of the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway, whereas treatment with PRP reactivated this molecular axis. Inhibition of the Nrf2/HO-1 pathway using the Nrf2 inhibitor brusatol or through Nrf2 gene silencing counteracted the effects of PRP in reducing the tenderness and thermal pain thresholds of OA rats. Additionally, PRP reduced the mRNA expression of IL-1ß, IL-6, tumor necrosis factor-alpha (TNF-α), and matrix metallopeptidase 13 (MMP-13) and the protein expression of B-cell lymphoma 2 (Bcl-2), Bcl-2 associated X-protein (Bax), and caspase-3. Furthermore, inflammation and apoptosis were induced by brusatol treatment or Nrf2 silencing. Additionally, in the in vitro model, PRP treatment increased the proliferation of chondrocytes and attenuated their inflammatory response and apoptosis, effects that were abrogated by Nrf2 depletion. CONCLUSIONS: The Nrf2/HO-1 pathway participates in the PRP-mediated attenuation of OA development by suppressing inflammation and apoptosis.


Asunto(s)
Apoptosis , Condrocitos , Factor 2 Relacionado con NF-E2 , Osteoartritis , Plasma Rico en Plaquetas , Transducción de Señal , Animales , Osteoartritis/terapia , Osteoartritis/metabolismo , Osteoartritis/patología , Factor 2 Relacionado con NF-E2/metabolismo , Factor 2 Relacionado con NF-E2/genética , Ratas , Condrocitos/metabolismo , Masculino , Antiinflamatorios/farmacología , Cuassinas/farmacología , Cuassinas/uso terapéutico , Ratas Sprague-Dawley , Modelos Animales de Enfermedad , Hemo-Oxigenasa 1/metabolismo , Hemo-Oxigenasa 1/genética , Hemo Oxigenasa (Desciclizante)/metabolismo , Hemo Oxigenasa (Desciclizante)/genética , Interleucina-1beta/metabolismo , Inflamación/inmunología , Células Cultivadas
7.
Med Oncol ; 41(7): 172, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38862702

RESUMEN

Resistance to caspase-dependent apoptosis is often responsible for treatments failure in cancer. Necroptosis is a type of programmed necrosis that occurs under caspase-deficient conditions that could overcome apoptosis resistance. Our purpose was to investigate the interrelationship between apoptotic and necroptotic death pathways and their influence on the response of breast cancer cells to radiotherapy in vitro. Human BC cell lines MCF-7 and MDA-MB-231 were treated with ionizing radiation, and then several markers of apoptosis, necroptosis, and survival were assessed in the presence and absence of necroptosis inhibition. MLKL knockdown was achieved by siRNA transfection. Our main findings emphasize the role of necroptosis in cellular response to radiation represented in the dose- and time-dependent elevated expression of necroptotic markers RIPK1, RIPK3, and MLKL. Knockdown of necroptotic marker MLKL by siRNA led to a significant elevation in MDA-MB-231 and MCF-7 survival with a dose modifying factor (DMF) of 1.23 and 1.61, respectively. Apoptotic markers Caspase 8 and TRADD showed transitory or delayed upregulation, indicating that apoptosis was not the main mechanism by which cells respond to radiation exposure. Apoptotic markers also showed a significant elevation following MLKL knockdown, suggesting its role either as a secondary or death alternative pathway. The result of our study emphasizes the critical role of the necroptotic pathway in regulating breast cancer cells responses to radiotherapy and suggests a promising utilization of its key modulator, MLKL, as a treatment strategy to improve the response to radiotherapy.


Asunto(s)
Apoptosis , Neoplasias de la Mama , Necroptosis , Proteínas Quinasas , Humanos , Apoptosis/efectos de la radiación , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/genética , Femenino , Proteínas Quinasas/metabolismo , Proteínas Quinasas/genética , Línea Celular Tumoral , ARN Interferente Pequeño/genética , Transducción de Señal , Células MCF-7
8.
Eur Rev Med Pharmacol Sci ; 28(10): 3473, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38856145

RESUMEN

The Editor in Chief and the Publisher are issuing an expression of concern to alert readers to the fact that the following articles are under investigation due to concerns raised regarding non-verifiable nucleotide sequences and cell lines used in the following articles: -       Shi YX, Ye BL, Hu BR, Ruan XJ. Expression of miR-1294 is downregulated and predicts a poor prognosis in gastric cancer. Eur Rev Med Pharmacol Sci 2018; 22 (17): 5525-5530-DOI: 10.26355/eurrev_201809_15813-PMID: 30229824. -       Dong SR, Ju XL, Yang WZ. STAT5A reprograms fatty acid metabolism and promotes tumorigenesis of gastric cancer cells. Eur Rev Med Pharmacol Sci 2019; 23 (19): 8360-8370-DOI: 10.26355/eurrev_201910_19147-PMID: 31646566. -       Chen J, Yuan ZH, Hou XH, Shi MH, Jiang R. LINC01116 promotes the proliferation and inhibits the apoptosis of gastric cancer cells. Eur Rev Med Pharmacol Sci 2020; 24 (4): 1807-1814-DOI: 10.26355/eurrev_202002_20358-PMID: 32141549. Further updates will be provided once the investigation is completed. The authors have been notified about this expression of concern.


Asunto(s)
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Neoplasias Gástricas/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Apoptosis , Proliferación Celular
10.
Oncotarget ; 15: 361-373, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38829622

RESUMEN

Histone deacetylase inhibitors (HDACi) can modulate the acetylation status of proteins, influencing the genomic instability exhibited by cancer cells. Poly (ADP ribose) polymerase (PARP) inhibitors (PARPi) have a direct effect on protein poly (ADP-ribosyl)ation, which is important for DNA repair. Decitabine is a nucleoside cytidine analogue, which when phosphorylated gets incorporated into the growing DNA strand, inhibiting methylation and inducing DNA damage by inactivating and trapping DNA methyltransferase on the DNA, thereby activating transcriptionally silenced DNA loci. We explored various combinations of HDACi and PARPi +/- decitabine (hypomethylating agent) in pancreatic cancer cell lines BxPC-3 and PL45 (wild-type BRCA1 and BRCA2) and Capan-1 (mutated BRCA2). The combination of HDACi (panobinostat or vorinostat) with PARPi (talazoparib or olaparib) resulted in synergistic cytotoxicity in all cell lines tested. The addition of decitabine further increased the synergistic cytotoxicity noted with HDACi and PARPi, triggering apoptosis (evidenced by increased cleavage of caspase 3 and PARP1). The 3-drug combination treatments (vorinostat, talazoparib, and decitabine; vorinostat, olaparib, and decitabine; panobinostat, talazoparib, and decitabine; panobinostat, olaparib, and decitabine) induced more DNA damage (increased phosphorylation of histone 2AX) than the individual drugs and impaired the DNA repair pathways (decreased levels of ATM, BRCA1, and ATRX proteins). The 3-drug combinations also altered the epigenetic regulation of gene expression (NuRD complex subunits, reduced levels). This is the first study to demonstrate synergistic interactions between the aforementioned agents in pancreatic cancer cell lines and provides preclinical data to design individualized therapeutic approaches with the potential to improve pancreatic cancer treatment outcomes.


Asunto(s)
Azacitidina , Decitabina , Sinergismo Farmacológico , Inhibidores de Histona Desacetilasas , Neoplasias Pancreáticas , Inhibidores de Poli(ADP-Ribosa) Polimerasas , Humanos , Decitabina/farmacología , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/metabolismo , Línea Celular Tumoral , Inhibidores de Histona Desacetilasas/farmacología , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Azacitidina/farmacología , Azacitidina/análogos & derivados , Apoptosis/efectos de los fármacos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología
11.
Cell Mol Life Sci ; 81(1): 247, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38829550

RESUMEN

BACKGROUND: The high degree of intratumoral genomic heterogeneity is a major obstacle for glioblastoma (GBM) tumors, one of the most lethal human malignancies, and is thought to influence conventional therapeutic outcomes negatively. The proneural-to-mesenchymal transition (PMT) of glioma stem cells (GSCs) confers resistance to radiation therapy in glioblastoma patients. POLD4 is associated with cancer progression, while the mechanisms underlying PMT and tumor radiation resistance have remained elusive. METHOD: Expression and prognosis of the POLD family were analyzed in TCGA, the Chinese Glioma Genome Atlas (CGGA) and GEO datasets. Tumorsphere formation and in vitro limiting dilution assay were performed to investigate the effect of UCHL3-POLD4 on GSC self-renewal. Apoptosis, TUNEL, cell cycle phase distribution, modification of the Single Cell Gel Electrophoresis (Comet), γ-H2AX immunofluorescence, and colony formation assays were conducted to evaluate the influence of UCHL3-POLD4 on GSC in ionizing radiation. Coimmunoprecipitation and GST pull-down assays were performed to identify POLD4 protein interactors. In vivo, intracranial xenograft mouse models were used to investigate the molecular effect of UCHL3, POLD4 or TCID on GCS. RESULT: We determined that POLD4 was considerably upregulated in MES-GSCs and was associated with a meagre prognosis. Ubiquitin carboxyl terminal hydrolase L3 (UCHL3), a DUB enzyme in the UCH protease family, is a bona fide deubiquitinase of POLD4 in GSCs. UCHL3 interacted with, depolyubiquitinated, and stabilized POLD4. Both in vitro and in vivo assays indicated that targeted depletion of the UCHL3-POLD4 axis reduced GSC self-renewal and tumorigenic capacity and resistance to IR treatment by impairing homologous recombination (HR) and nonhomologous end joining (NHEJ). Additionally, we proved that the UCHL3 inhibitor TCID induced POLD4 degradation and can significantly enhance the therapeutic effect of IR in a gsc-derived in situ xenograft model. CONCLUSION: These findings reveal a new signaling axis for GSC PMT regulation and highlight UCHL3-POLD4 as a potential therapeutic target in GBM. TCID, targeted for reducing the deubiquitinase activity of UCHL3, exhibited significant synergy against MES GSCs in combination with radiation.


Asunto(s)
Células Madre Neoplásicas , Tolerancia a Radiación , Ubiquitina Tiolesterasa , Humanos , Ubiquitina Tiolesterasa/metabolismo , Ubiquitina Tiolesterasa/genética , Tolerancia a Radiación/genética , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Células Madre Neoplásicas/efectos de la radiación , Animales , Ratones , Línea Celular Tumoral , Glioma/patología , Glioma/genética , Glioma/radioterapia , Glioma/metabolismo , Apoptosis/genética , Apoptosis/efectos de la radiación , Ubiquitinación , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/radioterapia , Ratones Desnudos , Fenotipo , Regulación Neoplásica de la Expresión Génica , Pronóstico
12.
Folia Biol (Praha) ; 70(1): 53-61, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38830123

RESUMEN

Psoriasis is a chronic non-contagious autoimmune disease. Gallic acid is a natural compound with potential health benefits, including antioxidant, anticancer, antiviral and antibacterial properties. Nevertheless, the influence of gallic acid on psoriasis has not been fully determined. This investigation aimed to discover the effect of gallic acid on psoriasis. Thirty-one pairs of psoriatic skin tissues and healthy adult human skin tissues were collected. Human keratinocytes (HaCaT cells) were transfected with interleukin 17A (IL-17A) to create the psoriatic keratinocyte model. The content of bromodomain-containing protein 4 (BRD4) microRNA was assessed using qRT-PCR testing. The content of BRD4 was detected by Western blotting. Cell migration was evaluated by conducting a wound healing assay. Cell proliferation was determined using an EdU assay. Apoptosis was detected by the TUNEL assay. The contents of interferon gamma (IFN-γ), IL-6, IL-8 and IL-17 were detected by ELISA. BRD4 was up-regulated in psoriatic skin tissues and in the IL-17A group compared to the healthy adult human skin tissues and the control group. Silencing BRD4 inhibited cell migration, proliferation and inflammatory response but induced apoptosis in IL-17A-treated HaCaT cells. Conversely, BRD4 over-expression promoted cell migration, proliferation and inflammatory response but suppressed apoptosis in IL-17A-treated HaCaT cells. Gallic acid repressed cell migration, proliferation and inflammatory response but indu-ced apoptosis in HaCaT cells transfected with IL-17A by down-regulating BRD4. Gallic acid represses cell migration, proliferation and inflammatory response but induces apoptosis in IL-17A-transfected HaCaT cells by down-regulating BRD4.


Asunto(s)
Apoptosis , Proteínas de Ciclo Celular , Movimiento Celular , Proliferación Celular , Ácido Gálico , Inflamación , Queratinocitos , Psoriasis , Factores de Transcripción , Humanos , Psoriasis/metabolismo , Psoriasis/patología , Psoriasis/tratamiento farmacológico , Factores de Transcripción/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Ácido Gálico/farmacología , Queratinocitos/efectos de los fármacos , Queratinocitos/metabolismo , Apoptosis/efectos de los fármacos , Inflamación/patología , Proliferación Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Interleucina-17/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Adulto , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Masculino , Células HaCaT , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Línea Celular , Proteínas que Contienen Bromodominio
13.
PLoS One ; 19(6): e0304701, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38870120

RESUMEN

This paper presents the initial exploration of the free radical scavenging capabilities of peptides derived from protein hydrolysates (PPH) obtained from Zingiber cassumunar rhizomes (Phlai). To replicate the conditions of gastrointestinal digestion, a combination of pepsin and pancreatin proteolysis was employed to generate these hydrolysates. Subsequently, the hydrolysate underwent fractionation using molecular weight cut-off membranes at 10, 5, 3, and 0.65 kDa. The fraction with a molecular weight less than 0.65 kDa exhibited the highest levels ABTS, DPPH, FRAP, and NO radical scavenging activity. Following this, RP-HPLC was used to further separate the fraction with a molecular weight less than 0.65 kDa into three sub-fractions. Among these, the F5 sub-fraction displayed the most prominent radical-scavenging properties. De novo peptide sequencing via quadrupole-time-of-flight-electron spin induction-mass spectrometry identified a pair of novel peptides: Asp-Gly-Ile-Phe-Val-Leu-Asn-Tyr (DGIFVLNY or DY-8) and Ile-Pro-Thr-Asp-Glu-Lys (IPTDEK or IK-6). Database analysis confirmed various properties, including biological activity, toxicity, hydrophilicity, solubility, and potential allergy concerns. Furthermore, when tested on the human adenocarcinoma colon (Caco-2) cell line, two synthetic peptides demonstrated cellular antioxidant activity in a concentration-dependent manner. These peptides were also assessed using the FITC Annexin V apoptosis detection kit with PI, confirming the induction of apoptosis. Notably, the DY-8 peptide induced apoptosis, upregulated mRNA levels of caspase-3, -8, and -9, and downregulated Bcl-2, as confirmed by real-time quantitative polymerase chain reaction (RT-qPCR). Western blot analysis indicated increased pro-apoptotic Bax expression and decreased anti-apoptotic Bcl-2 expression in Caco-2 cells exposed to the DY-8 peptide. Molecular docking analysis revealed that the DY-8 peptide exhibited binding affinity with Bcl-2, Bcl-xL, and Mcl-1, suggesting potential utility in combating colon cancer as functional food ingredients.


Asunto(s)
Apoptosis , Neoplasias del Colon , Péptidos , Rizoma , Transducción de Señal , Humanos , Apoptosis/efectos de los fármacos , Rizoma/química , Células CACO-2 , Transducción de Señal/efectos de los fármacos , Péptidos/farmacología , Péptidos/química , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/patología , Neoplasias del Colon/metabolismo , Zingiberaceae/química , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/patología , Adenocarcinoma/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/química , Depuradores de Radicales Libres/farmacología , Depuradores de Radicales Libres/química
14.
Reprod Fertil Dev ; 362024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38870343

RESUMEN

Context Carbon tetrachloride (CCl4 ) is a chemical that is still widely used in industry and has been shown to cause structural defects in rat testicles through oxidative stress. Aims In our study, the effect of curcumin on CCl4 -mediated testicular damage was investigated. Methods Twenty-four adult Wistar albino male rats weighing 300-350g were divided into four groups: control group (olive oil was applied by gavage every consecutive day for 3weeks); curcumin and CCl4 +curcumin groups (200mg/kg curcumin dissolved in olive oil was given by gavage once a day, every consecutive day for 3weeks); and CCl4 and CCl4 +curcumin groups (0.5mL/kg CCl4 was dissolved in olive oil at a ratio of 1/1 and given by i.p. injection every other day for 3weeks). Tissue samples were examined histopathologically, histomorphometrically, immunohistochemically and biochemically. Key results CCl4 disrupted both testicular morphology and testosterone synthesis, whereas curcumin treatment resulted in an improvement in testicular morphology and biochemical parameters, as well as a decrease in caspase-3 and tumour necrosis factor-α expression. Conclusions Curcumin has a protective effect on testicular tissue damage caused by CCl4 with its anti-inflammatory, antiapoptotic and antioxantioxidant properties. Implications Curcumin can prevent testicular damage due to CCl4 , an environmental pollutant.


Asunto(s)
Tetracloruro de Carbono , Curcumina , Estrés Oxidativo , Ratas Wistar , Testículo , Testosterona , Animales , Masculino , Curcumina/farmacología , Testículo/efectos de los fármacos , Testículo/patología , Testículo/metabolismo , Testosterona/sangre , Ratas , Estrés Oxidativo/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismo , Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Caspasa 3/metabolismo , Enfermedades Testiculares/prevención & control , Enfermedades Testiculares/patología , Enfermedades Testiculares/inducido químicamente , Enfermedades Testiculares/metabolismo
15.
Sci Rep ; 14(1): 13625, 2024 06 13.
Artículo en Inglés | MEDLINE | ID: mdl-38871787

RESUMEN

Currently, the increasing pollution of the environment by heavy metals is observed, caused both by natural factors and those related to human activity. They pose a significant threat to human health and life. It is therefore important to find an effective way of protecting organisms from their adverse effects. One potential product showing a protective effect is green tea. It has been shown that EGCG, which is found in large amounts in green tea, has strong antioxidant properties and can therefore protect cells from the adverse effects of heavy metals. Therefore, the aim of the study was to investigate the effect of EGCG on cells exposed to Cd. In the study, CHO-K1 cells (Chinese hamster ovary cell line) were treated for 24 h with Cd (5 and 10 µM) and EGCG (0.5 and 1 µM) together or separately. Cell viability, ATP content, total ROS activity, mitochondrial membrane potential and apoptosis potential were determined. The results showed that, in tested concentrations, EGCG enhanced the negative effect of Cd. Further analyses are needed to determine the exact mechanism of action of EGCG due to the small number of publications on the subject and the differences in the results obtained in the research.


Asunto(s)
Apoptosis , Cadmio , Catequina , Supervivencia Celular , Cricetulus , Potencial de la Membrana Mitocondrial , Estrés Oxidativo , Especies Reactivas de Oxígeno , Catequina/análogos & derivados , Catequina/farmacología , Animales , Células CHO , Apoptosis/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Cadmio/toxicidad , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Supervivencia Celular/efectos de los fármacos , Antioxidantes/farmacología , Cricetinae , Adenosina Trifosfato/metabolismo
16.
J Cancer Res Clin Oncol ; 150(6): 305, 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38871970

RESUMEN

PURPOSE: The copper metabolism MURR1 domain 10 (COMMD10) plays a role in a variety of tumors. Here, we investigated its role in gastric cancer (GC). METHODS: Online prediction tools, quantitative real-time PCR, western blotting and immunohistochemistry were used to evaluate the expression of COMMD10 in GC. The effect of COMMD10 knockdown was investigated in the GC cell lines and in in vivo xenograft tumor experiments. Western blotting and immunofluorescence were used to explore the relationships between COMMD10 and DNA damage. RESULTS: The expression of COMMD10 was upregulated in GC compared to that in para-cancerous tissue and correlated with a higher clinical TNM stage (P = 0.044) and tumor size (P = 0.0366). High COMMD10 expression predicted poor prognosis in GC. Knockdown of COMMD10 resulted in the suppression of cell proliferation, migration, and invasion, accompanied by cell cycle arrest and an elevation in apoptosis rate. Moreover, the protein expression of COMMD10 was decreased in cisplatin-induced DNA-damaged GC cells. Suppression of COMMD10 impeded DNA damage repair, intensified DNA damage, and activated ATM-p53 signaling pathway in GC. Conversely, restoration of COMMD10 levels suppressed DNA damage and activation of the ATM-p53 signaling cascade. Additionally, knockdown of COMMD10 significantly restrained the growth of GC xenograft tumors while inhibiting DNA repair, augmenting DNA damage, and activating the ATM-p53 signaling pathway in xenograft tumor tissue. CONCLUSION: COMMD10 is involved in DNA damage repair and maintains genomic stability in GC; knockdown of COMMD10 impedes the development of GC by exacerbating DNA damage, suggesting that COMMD10 may be new target for GC therapy.


Asunto(s)
Proliferación Celular , Daño del ADN , Progresión de la Enfermedad , Neoplasias Gástricas , Neoplasias Gástricas/patología , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Humanos , Animales , Ratones , Femenino , Masculino , Ratones Desnudos , Línea Celular Tumoral , Apoptosis , Pronóstico , Persona de Mediana Edad , Ensayos Antitumor por Modelo de Xenoinjerto , Ratones Endogámicos BALB C , Movimiento Celular , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Regulación Neoplásica de la Expresión Génica
17.
Mol Biol Rep ; 51(1): 732, 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38872006

RESUMEN

BACKGROUND: The present study aimed to elucidate the potential anticancer activity and mechanism of P. harmala's alkaloid extract, harmine (HAR), and harmaline (HAL) in HCT-116 colorectal cancer cells. METHODS AND RESULTS: P. harmala's alkaloid was extracted from harmala seeds. HCT-116 cells were treated with P. harmala's alkaloid extract, HAR and HAL. Cytotoxicity was determined by MTT assay, apoptotic activity detected via flow cytometry and acridine orange (AO)/ethidium bromide (EB) dual staining, and cell cycle distribution analyzed with flow cytometry. The mRNA expression of Bcl-2-associated X protein (Bax) and glycogen synthase kinase-3 beta (GSK3ß) was measured by real-time PCR. Furthermore, the expression of Bax, Bcl-2, GSK3ß and p53 proteins, were determined by western blotting. The findings indicated that, P. harmala's alkaloids extract, HAR and HAL were significantly cytotoxic toward HCT116 cells after 24 and 48 h of treatment. We showed that P. harmala's alkaloid extract induce apoptosis and cell cycle arrest at G2 phase in the HCT116 cell line. Downregulation of GSK3ß and Bcl-2 and upregulation of Bax and p53 were observed. CONCLUSION: The findings of this study indicate that the P. harmala's alkaloid extract has anticancer activity and may be further investigated to develop future anticancer chemotherapeutic agents.


Asunto(s)
Apoptosis , Neoplasias del Colon , Glucógeno Sintasa Quinasa 3 beta , Harmina , Peganum , Semillas , Humanos , Peganum/química , Células HCT116 , Apoptosis/efectos de los fármacos , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/metabolismo , Neoplasias del Colon/patología , Semillas/química , Harmina/farmacología , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Proteína X Asociada a bcl-2/metabolismo , Proteína X Asociada a bcl-2/genética , Extractos Vegetales/farmacología , Extractos Vegetales/química , Alcaloides/farmacología , Harmalina/farmacología , Antineoplásicos Fitogénicos/farmacología , Proteína p53 Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proliferación Celular/efectos de los fármacos
18.
BMC Cancer ; 24(1): 726, 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38872110

RESUMEN

Polysaccharopeptide (PSP) is a potential active component in traditional Chinese medicine because of its anticancer effects on a variety of cancer cells and as immune enhancers of the immune system. Previous studies on the role of PSP in breast cancer have been limited, and the mechanism has not been clarified. This study is based on network pharmacology and molecular docking technology to predict the possible target of PSP treatment of breast cancer, and use experiments to verify the effect and mechanism of PSP on breast cancer. In this study, 287 PSP targets were obtained using SwissTargetPrediction database and PharmMapper database, and 183 breast cancer targets were obtained using DisGenNET database. By intersections of PSP targets and breast cancer targets, a total of 10 intersections were obtained. GO functional enrichment, KEGG pathway enrichment and molecular docking of these 10 target genes were performed to obtain the potential targets of PSP on breast cancer. In vitro experiments, we found that PSP significantly inhibited the proliferation and induced apoptosis of breast cancer cell lines MDA-MB-231, SUM-159 and MCF-7. Western Blot results showed that PSP could down-regulate the expression of p-JAK2 and p-STAT3 proteins. Similarly, the results of in vivo experiments showed that PSP can directly inhibit the tumor of MDA-MB-231 tumor-bearing mice, and the mechanism of action is mainly to inhibit the JAK2-STAT3 pathway. The above results were consistent with the results of network pharmacology, which provides a scientific basis for the clinical application of PSP in breast cancer patients.


Asunto(s)
Apoptosis , Neoplasias de la Mama , Proliferación Celular , Janus Quinasa 2 , Simulación del Acoplamiento Molecular , Farmacología en Red , Factor de Transcripción STAT3 , Ensayos Antitumor por Modelo de Xenoinjerto , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Femenino , Animales , Ratones , Proliferación Celular/efectos de los fármacos , Apoptosis/efectos de los fármacos , Factor de Transcripción STAT3/metabolismo , Línea Celular Tumoral , Janus Quinasa 2/metabolismo , Proteoglicanos/farmacología , Células MCF-7 , Ratones Desnudos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Transducción de Señal/efectos de los fármacos
19.
Cancer Med ; 13(11): e7395, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38872370

RESUMEN

BACKGROUND AND AIMS: Pancreatic cancer is one of the most lethal malignancies, partly due to resistance to conventional chemotherapy. The chemoresistance of malignant tumors is associated with epithelial-mesenchymal transition (EMT) and the stemness of cancer cells. The aim of this study is to investigate the availability and functional mechanisms of trefoil factor family 1 (TFF1), a tumor-suppressive protein in pancreatic carcinogenesis, to treat pancreatic cancer. METHODS: To investigate the role of endogenous TFF1 in human and mice, specimens of human pancreatic cancer and genetically engineered mouse model of pancreatic cancer (KPC/TFF1KO; Pdx1-Cre/LSL-KRASG12D/LSL-p53R172H/TFF1-/-) were analyzed by immunohistochemistry (IHC). To explore the efficacy of extracellular administration of TFF1, recombinant and chemically synthesized TFF1 were administered to pancreatic cancer cell lines, a xenograft mouse model and a transgenic mouse model. RESULTS: The deficiency of TFF1 was associated with increased EMT of cancer cells in mouse models of pancreatic cancer, KPC. The expression of TFF1 in cancer cells was associated with better survival rate of the patients who underwent chemotherapy, and loss of TFF1 deteriorated the benefit of gemcitabine in KPC mice. Extracellular administration of TFF1 inhibited gemcitabine-induced EMT, Wnt pathway activation and cancer stemness, eventually increased apoptosis of pancreatic cancer cells in vitro. In vivo, combined treatment of gemcitabine and subcutaneous administration of TFF1 arrested tumor growth in xenograft mouse model and resulted in the better survival of KPC mice by inhibiting EMT and cancer stemness. CONCLUSION: These results indicate that TFF1 can contribute to establishing a novel strategy to treat pancreatic cancer patients by enhancing chemosensitivity.


Asunto(s)
Resistencia a Antineoplásicos , Transición Epitelial-Mesenquimal , Células Madre Neoplásicas , Neoplasias Pancreáticas , Factor Trefoil-1 , Animales , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/genética , Factor Trefoil-1/metabolismo , Factor Trefoil-1/genética , Humanos , Ratones , Transición Epitelial-Mesenquimal/efectos de los fármacos , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/efectos de los fármacos , Línea Celular Tumoral , Proteínas Supresoras de Tumor/metabolismo , Proteínas Supresoras de Tumor/genética , Ensayos Antitumor por Modelo de Xenoinjerto , Gemcitabina , Ratones Transgénicos , Femenino , Masculino , Proliferación Celular/efectos de los fármacos , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacología , Desoxicitidina/uso terapéutico , Apoptosis/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos
20.
Cancer Med ; 13(11): e7382, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38872380

RESUMEN

BACKGROUND: Colorectal cancer (CRC) ranks among the most prevalent malignancies worldwide, characterized by its complex etiology and slow research progress. Diabetes, as an independent risk factor for CRC, has been widely certified. Consequently, this study centers on elucidating the intricacies of CRC cells initiation and progression within a high-glucose environment. METHODS: A battery of assays was employed to assess the proliferation and metastasis of CRC cells cultured under varying glucose concentrations. Optimal glucose levels conducive to cells' proliferation and migration were identified. Western blot analyses were conducted to evaluate alterations in apoptosis, autophagy, and EMT-related proteins in CRC cells under high-glucose conditions. The expression of PI3K/AKT/mTOR pathway-associated proteins was assessed using western blot. The effect of high glucose on xenograft growth was investigated in vivo by MC38 cells, and changes in inflammatory factors (IL-4, IL-13, TNF-α, IL-5, and IL-12) were measured via serum ELISA. RESULTS: Our experiments demonstrated that elevated glucose concentrations promoted both the proliferation and migration of CRC cells; the most favorable glucose dose is 20 mM. Western blot analyses revealed a decrease in apoptotic proteins, such as Bim, Bax, and caspase-3 with increasing glucose levels. Concurrently, the expression of EMT-related proteins, including N-cadherin, vimentin, ZEB1, and MMP9, increased. High-glucose cultured cells exhibited elevated levels of PI3K/AKT/mTOR pathway proteins. In the xenograft model, tumor cells stimulated by high glucose exhibited accelerated growth, larger tumor volumes, and heightened KI67 expression of immunohistochemistry. ELISA experiments revealed higher expression of IL-4 and IL-13 and lower expression of TNF-α and IL-5 in the serum of high-glucose-stimulated mice. CONCLUSION: The most favorable dose and time for tumor cells proliferation and migration is 20 mM, 48 h. High glucose fosters CRC cell proliferation and migration while suppressing autophagy through the activation of the PI3K/AKT/mTOR pathway.


Asunto(s)
Autofagia , Movimiento Celular , Proliferación Celular , Neoplasias Colorrectales , Glucosa , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Serina-Treonina Quinasas TOR , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Animales , Proliferación Celular/efectos de los fármacos , Humanos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Autofagia/efectos de los fármacos , Glucosa/metabolismo , Ratones , Transducción de Señal/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Apoptosis/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto , Metástasis de la Neoplasia
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