RESUMEN
Herein, luminous blue carbon quantum dots (CDs) employing Anisomeles indica (Catmint) were reported with imaging, self-targeting, and therapeutic effects on triple-negative breast cancer (TNBC, MDA-MB-231) cells. The salient features of CDs generated from catmint are as follows: i) optical studies confirm CDs with excitation-dependent emission; ii) high-throughput characterization authenticates the formation of CDs with near-spherical shape with diameter ranging between 5 and 15 nm; iii) CDs induce cytotoxicity (3.22 ± 0.64 µg/ml) in triple-negative breast cancer (TNBC, MDA-MB-231) cells; iv) fluorescence microscopy demonstrates that CDs promote apoptosis by increasing reactive oxygen species (ROS) and decreasing mitochondrial membrane potential; v) CDs significantly up-regulate pro-apoptotic gene expression levels such as caspases-8/9/3. Finally, our work demonstrates that catmint-derived CDs are prospective nanotheranostics that augment cancer targeting and imaging.
Asunto(s)
Apoptosis , Carbono , Puntos Cuánticos , Transducción de Señal , Neoplasias de la Mama Triple Negativas , Puntos Cuánticos/química , Humanos , Apoptosis/efectos de los fármacos , Neoplasias de la Mama Triple Negativas/metabolismo , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Carbono/química , Carbono/farmacología , Transducción de Señal/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Lamiaceae/química , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Antineoplásicos/farmacología , Antineoplásicos/químicaRESUMEN
BACKGROUND/AIMS: Traumatic brain injury is a significant public problem with an incidence of 10 million people per year, causing the largest deaths and disabilities worldwide. Head injuries can be classified into primary and secondary head injuries. Secondary head injuries can be caused by several factors such as ischemia, cerebral edema, and neuroinflammation. AIF and MMP-9 are two parameters that can be indicators in measuring the effect of Oleuropein on traumatic brain injury in rats. Oleuropein itself has many activities such as antioxidant, anti-apoptotic, antimicrobial, anti-inflammatory, and neuroprotective. METHODS: Adult male Sprague-Dawley rats (250-350 grams) were exposed to head injury, with or without intraperitoneal administration of Oleuropein. Within 24-72 hours brain tissue was isolated for immunohistochemical analysis, ELISA, and TUNEL. AIF, GFAP, MMP-9, and HMGB-1 levels were determined using immunohistochemistry in both the control and treatment groups. Statistical analysis was made using the One-Way Analysis of Variance (ANOVA) and paired t-test. RESULTS: The results showed that Oleuropein was able to reduce AIF and MMP-9 levels in rats with traumatic brain injury. This indicates that Oleuropein has a neuroprotective effect by reducing inflammation and apoptosis. CONCLUSION: Oleuropein has a potential neuroprotective effect in traumatic brain injury by reducing inflammation and apoptosis. Therefore, Oleuropein can be considered as a potential therapeutic agent for traumatic brain injury in the future.
Asunto(s)
Factor Inductor de la Apoptosis , Lesiones Traumáticas del Encéfalo , Modelos Animales de Enfermedad , Glucósidos Iridoides , Iridoides , Metaloproteinasa 9 de la Matriz , Ratas Sprague-Dawley , Animales , Glucósidos Iridoides/farmacología , Glucósidos Iridoides/uso terapéutico , Metaloproteinasa 9 de la Matriz/metabolismo , Masculino , Lesiones Traumáticas del Encéfalo/metabolismo , Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Lesiones Traumáticas del Encéfalo/patología , Iridoides/farmacología , Iridoides/uso terapéutico , Ratas , Factor Inductor de la Apoptosis/metabolismo , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Proteína HMGB1/metabolismo , Apoptosis/efectos de los fármacos , Proteína Ácida Fibrilar de la Glía/metabolismo , Encéfalo/metabolismo , Encéfalo/patología , Encéfalo/efectos de los fármacosRESUMEN
Mushrooms produce many metabolites that show biological activity, which can be obtained from their fruiting body, mycelium or recovered from the culture broth when mushrooms are grown in submerged fermentation. Mushrooms are a source of natural pharmaceuticals; they have been reported to have potential inhibitory or preventive activity against some diseases, including different types of cancer. Cancer represents one of the main causes of death worldwide. It is worth mentioning that despite advances in pharmacological treatments, they still present side effects in patients. In this sense, the study of the use of mushrooms in complementary treatments against cancer is of great interest. Based on studies carried out in vitro and, in some cases, using animal models, it has been observed that mushrooms present preventive, corrective, and therapeutic properties against different types of cancer, by stimulating the immune system, due to their antioxidant, antimutagenic, and anti-inflammatory activities, as well as the regulation of the expression of some cellular processes, cell cycle arrest, and apoptosis, etc. Based on the above, this manuscript shows a review of scientific studies that support the anticancer activity of some mushrooms and/or their bioactive compounds.
Asunto(s)
Agaricales , Antineoplásicos , Agaricales/química , Humanos , Antineoplásicos/farmacología , Antineoplásicos/química , Animales , Neoplasias/tratamiento farmacológico , Productos Biológicos/farmacología , Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Antiinflamatorios/farmacologíaRESUMEN
Anesthetic-induced developmental neurotoxicity (AIDN) can arise due to various factors, among which aberrant nerve cell death is a prominent risk factor. Animal studies have reported that repeated or prolonged anesthetic exposure can cause significant neuroapoptosis in the developing brain. Lately, non-apoptotic programmed cell deaths (PCDs), characterized by inflammation and oxidative stress, have gained increasing attention. Substantial evidence suggests that non-apoptotic PCDs are essential for neuronal cell death in AIDN compared to apoptosis. This article examines relevant publications in the PubMed database until April 2024. Only original articles in English that investigated the potential manifestations of non-apoptotic PCD in AIDN were analysed. Specifically, it investigates necroptosis, pyroptosis, ferroptosis, and parthanatos, elucidating the signaling mechanisms associated with each form. Furthermore, this study explores the potential relevance of these non-apoptotic PCDs pathways to the pathological mechanisms underlying AIDN, drawing upon their distinctive characteristics. Despite the considerable challenges involved in translating fundamental scientific knowledge into clinical therapeutic interventions, this comprehensive review offers a theoretical foundation for developing innovative preventive and treatment strategies targeting non-apoptotic PCDs in the context of AIDN.
Asunto(s)
Anestésicos , Apoptosis , Síndromes de Neurotoxicidad , Humanos , Síndromes de Neurotoxicidad/patología , Síndromes de Neurotoxicidad/etiología , Animales , Anestésicos/efectos adversos , Anestésicos/toxicidad , Anestésicos/farmacología , Apoptosis/efectos de los fármacos , Neuronas/efectos de los fármacos , Neuronas/patología , Neuronas/metabolismo , Piroptosis/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Necroptosis/efectos de los fármacos , Encéfalo/efectos de los fármacos , Encéfalo/patología , Encéfalo/crecimiento & desarrollo , Ferroptosis/efectos de los fármacos , Transducción de Señal/efectos de los fármacosRESUMEN
Muscle invasive bladder cancers (BCs) can be divided into 2 major subgroups-basal/squamous (BASQ) tumors and luminal tumors. Since Pparg has low or undetectable expression in BASQ tumors, we tested the effects of rosiglitazone, Pparg agonist, in a mouse model of BASQ BC. We find that rosiglitazone reduces proliferation while treatment with rosiglitazone plus trametinib, a MEK inhibitor, induces apoptosis and reduces tumor volume by 91% after 1 month. Rosiglitazone and trametinib also induce a shift from BASQ to luminal differentiation in tumors, which our analysis suggests is mediated by retinoid signaling, a pathway known to drive the luminal differentiation program. Our data suggest that rosiglitazone, trametinib, and retinoids, which are all FDA approved, may be clinically active in BASQ tumors in patients.
Asunto(s)
Apoptosis , Proliferación Celular , Modelos Animales de Enfermedad , Piridonas , Pirimidinonas , Rosiglitazona , Neoplasias de la Vejiga Urinaria , Animales , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/genética , Piridonas/farmacología , Piridonas/uso terapéutico , Pirimidinonas/farmacología , Pirimidinonas/uso terapéutico , Rosiglitazona/farmacología , Rosiglitazona/uso terapéutico , Ratones , Apoptosis/efectos de los fármacos , Humanos , Proliferación Celular/efectos de los fármacos , Línea Celular Tumoral , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Invasividad Neoplásica , Femenino , PPAR gamma/metabolismo , PPAR gamma/agonistas , Tiazolidinedionas/farmacología , Tiazolidinedionas/uso terapéutico , Diferenciación Celular/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Retinoides/farmacología , Retinoides/uso terapéuticoRESUMEN
BACKGROUND: Type 1 diabetes mellitus (T1DM) is characterized by immune and metabolic dysregulation. Apo1/Fas is implicated in maintaining homeostasis of the immune system. Cytokeratin-18 (cCK-18) is a predictive marker of liver disorders in T2DM. Intercellular adhesion molecule-1 (ICAM-1) is considered to increase susceptibility to diabetes mellitus. All three markers are associated with endothelial function, apoptosis and diabetes-related complications. The possible role of Apo1/Fas, cCK-18 and ICAM-1 was investigated in children and adolescents with T1DM. METHOD: Forty-nine (49) children and adolescents with T1DM and 49 controls were included in the study. Somatometric measurements were obtained and the Body Mass Index (BMI) of the participants was calculated. Biochemical parameters were measured by standard laboratory methods and Apo1/Fas, cCK-18 and ICAM-1 were measured using appropriate ELISA kits. The statistical analysis was performed using the IBM SPSS Statistics 23 program. RESULTS: Apo1/Fas (p = 0.001), cCK-18 (p < 0.001) and ICAM-1 (p < 0.001) were higher in patients with T1DM compared to the controls. Apo1Fas was negatively correlated with glucose (p = 0.042), uric acid (p = 0.026), creatinine (p = 0.022), total cholesterol (p = 0.023) and LDL (p = 0.005) in the controls. In children and adolescents with T1DM, Apo1/Fas was positively correlated with total cholesterol (p = 0.013) and LDL (p = 0.003). ICAM-1 was negatively correlated with creatinine (p = 0.019) in the controls, whereas in patients with T1DM it was negatively correlated with HbA1c (p = 0.05). CONCLUSIONS: Apo1/Fas, cCK-18 and ICAM-1 may be useful as serological markers for immune and metabolic dysregulation in children and adolescents with T1DM. Also, Apo1/Fas may have a protective role against metabolic complications in healthy children.
Asunto(s)
Biomarcadores , Diabetes Mellitus Tipo 1 , Molécula 1 de Adhesión Intercelular , Humanos , Diabetes Mellitus Tipo 1/sangre , Molécula 1 de Adhesión Intercelular/sangre , Niño , Adolescente , Masculino , Femenino , Biomarcadores/sangre , Estudios de Casos y Controles , Queratina-18/sangre , Receptor fas/sangre , Apoptosis , Apolipoproteína A-I/sangreRESUMEN
The study investigates the therapeutic effects and mechanisms of ginsenoside Rg_1(GRg_1) on sepsis-induced acute lung injury(SALI). A murine model of SALI was created using cecal ligation and puncture(CLP) surgery, and mice were randomly assigned to groups for GRg_1 intervention. Survival and body weight changes were recorded, lung function was assessed with a non-invasive lung function test system, and lung tissue damage was evaluated through HE staining. The content and expression of inflammatory factors were measured by ELISA and qRT-PCR. Apoptosis was examined using flow cytometry and TUNEL staining. The activation and expression of apoptosis-related molecules cysteinyl aspartate specific proteinase 3(caspase-3), B-cell lymphoma-2(Bcl-2), Bcl-2 associated X protein(Bax), and endoplasmic reticulum stress-related molecules protein kinase R-like endoplasmic reticulum kinase(PERK), eukaryotic initiation factor 2α(eIF2α), activating transcription factor 4(ATF4), and C/EBP homologous protein(CHOP) were studied using Western blot and qRT-PCR. In addition, an in vitro model of lipopolysaccharide(LPS)-induced lung alveolar epithelial cell injury was used, with the application of the endoplasmic reticulum stress inducer tunicamycin to validate the action mechanism of GRg_1. RESULTS:: indicated that, when compared to the model group, GRg_1 intervention significantly enhanced the survival time of CLP mice, mitigated body weight loss, and improved impaired lung function indices. The GRg_1-treated mice also displayed reduced lung tissue pathological scores, a reduced lung tissue wet-to-dry weight ratio, and lower protein content in the bronchoalveolar lavage fluid. Serum levels of interleukin-6(IL-6), interleukin-1ß(IL-1ß), and tumor necrosis factor-α(TNF-α), as well as the mRNA expressions of these cytokines in lung tissues, were decreased. There was a notable decrease in the proportion of apopto-tic alveolar epithelial cells, and down-regulated expressions of caspase-3, Bax, PERK, eIF2α, ATF4, and CHOP and up-regulated expression of Bcl-2 were observed. In vitro findings showed that the apoptosis-lowering and apoptosis-related protein down-regulating effects of GRg_1 were significantly inhibited with the co-application of tunicamycin. Altogether, GRg_1 reduces apoptosis of alveolar epithelial cells, inhibits inflammation in the lungs, alleviates lung injury, and enhances lung function, possibly through the PERK/eIF2α/ATF4/CHOP pathway.
Asunto(s)
Factor de Transcripción Activador 4 , Lesión Pulmonar Aguda , Células Epiteliales Alveolares , Apoptosis , Factor 2 Eucariótico de Iniciación , Ginsenósidos , Sepsis , Factor de Transcripción CHOP , eIF-2 Quinasa , Animales , Lesión Pulmonar Aguda/tratamiento farmacológico , Lesión Pulmonar Aguda/metabolismo , Lesión Pulmonar Aguda/genética , Ginsenósidos/farmacología , Factor de Transcripción Activador 4/metabolismo , Factor de Transcripción Activador 4/genética , Ratones , Apoptosis/efectos de los fármacos , Factor de Transcripción CHOP/metabolismo , Factor de Transcripción CHOP/genética , Sepsis/tratamiento farmacológico , Sepsis/complicaciones , Sepsis/metabolismo , Sepsis/genética , eIF-2 Quinasa/metabolismo , eIF-2 Quinasa/genética , Factor 2 Eucariótico de Iniciación/metabolismo , Factor 2 Eucariótico de Iniciación/genética , Masculino , Células Epiteliales Alveolares/efectos de los fármacos , Células Epiteliales Alveolares/metabolismo , Humanos , Estrés del Retículo Endoplásmico/efectos de los fármacos , Ratones Endogámicos C57BLRESUMEN
The study investigated the effect of Compound Shougong Powder(CSGP) on the biological functions of triple-negative breast cancer(TNBC) cells and whether its mechanism of action was related to the epithelial-mesenchymal transition(EMT) signaling pathway. TNBC cells(MDA-MB-231 and BT-549) were treated with different concentrations of CSGP-containing serum. MTS assay was used to detect the effect of CSGP on the proliferation of TNBC cells. The EdU staining was used to detect the effect of CSGP on the proliferation of TNBC cells. Flow cytometry was used to examine the impact of CSGP on apoptosis of TNBC cells. Wound-healing and Transwell assays were used to evaluate the effects of different concentrations of CSGP on the migration and invasion capabilities of TNBC cells. RNA sequencing technology was utilized to elucidate its mechanism. Subsequently, qRT-PCR was performed to measure the mRNA expression levels of E-cadherin, N-cadherin, Slug, Snail, Vimentin, Twist, Zinc finger E-box-Binding homeobox 1(Zeb1), and Zinc finger E-box-Binding homeobox 2(Zeb2). Western blot was used to assess the protein expression levels of Slug, Vimentin, and E-cadherin. After intervention with CSGP, the proliferation of MDA-MB-231 and BT-549 cells significantly decreased, while the apoptosis rate markedly increased. The expression levels of the epithelial marker protein E-cadherin significantly increased, while the expression levels of the EMT-related transcription factors Slug and Vimentin showed a decrease. In conclusion, CSGP inhibits the EMT, thereby suppressing the malignant progression of TNBC.
Asunto(s)
Apoptosis , Proliferación Celular , Medicamentos Herbarios Chinos , Transición Epitelial-Mesenquimal , Neoplasias de la Mama Triple Negativas , Transición Epitelial-Mesenquimal/efectos de los fármacos , Humanos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/metabolismo , Neoplasias de la Mama Triple Negativas/patología , Medicamentos Herbarios Chinos/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Femenino , Apoptosis/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Polvos/química , Cadherinas/genética , Cadherinas/metabolismoRESUMEN
This paper investigated the effect of total saponins from Rhizoma Panacis Majoris on the proliferation, apoptosis, and autophagy of human cervical carcinoma HeLa cells. The saponin content was detected by ultraviolet-visible spectrophotometry. Cell coun-ting kit-8(CCK-8) assay, 4,6-diamidino-2-phenylindole(DAPI) staining, and flow cytometry were used to detect the effects of total saponins of Panacis Majoris Rhizoma on cell viability, morphology, cell cycle and apoptosis of HeLa cells. Western blot was used to detect the expression of apoptosis-related proteins B cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), cleaved caspase-9, and cleaved caspase-3, autophagy-related proteins Beclin-1 and SQSTM1(p62), and the proteins related to the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/Akt/mTOR) and mitogen-activated protein kinase(MAPK) signaling pathways. It was found that the yield and saponin content of total saponins from Rhizoma Panacis Majoris were 6.3% and 78.3%, respectively. Total saponins from Rhizoma Panacis Majoris could significantly inhibit the proliferation(P<0.001), effect the nuclear morphology, block the G_0/G_1 cycle, and induce cell apoptosis in HeLa cells with a concentration-dependent manner. In addition, total saponins from Rhizoma Panacis Majoris up-regulated the expression of pro-apoptotic proteins Bax, cleaved caspase-9, and cleaved caspase-3, and autophagy-related protein p62(P<0.05), while down-regulated the expression of anti-apoptotic protein Bcl-2 and autophagy-related protein Beclin-1(P<0.01). Total saponins from Rhizoma Panacis Majoris could promote the expression of p-p38/p38, p-Jun N-terminal kinase(JNK)/JNK, p-PI3K/PI3K, p-Akt/Akt, p-mTOR/mTOR proteins in PI3K/Akt/mTOR and MAPK signaling pathways(P<0.05). In contrast, the effect on p-ERK/ERK expression was not obvious. Therefore, total saponins from Rhizoma Panacis Majoris may inhibit autophagy and promote apoptosis of HeLa cells through the activation of the PI3K/Akt/mTOR, c-JNK, and p38 MAPK signaling pathways, which indicates that total saponins from Rhizoma Panacis Majoris may have a potential role in cervical cancer treatment.
Asunto(s)
Apoptosis , Autofagia , Proliferación Celular , Rizoma , Saponinas , Neoplasias del Cuello Uterino , Humanos , Saponinas/farmacología , Saponinas/química , Células HeLa , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Autofagia/efectos de los fármacos , Rizoma/química , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/patología , Femenino , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Transducción de Señal/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismo , Serina-Treonina Quinasas TOR/genética , Supervivencia Celular/efectos de los fármacosRESUMEN
The study investigated the protective effect and mechanism of 2-phenylethyl-beta-glucopyranoside(Phe) from Huaizhong No.1 Rehmannia glutinosa on hypoxic pulmonary hypertension(PH), aiming to provide a theoretical basis for clinical treatment of PAH. Male C57BL/6N mice were randomly divided into normal group, model group, positive drug(bosentan, 100 mg·kg~(-1)) group, and low-and high-dose Phe groups(20 and 40 mg·kg~(-1)). Except for the normal group, all other groups were continuously subjected to model induction in a 10% hypoxic environment for 5 weeks, with oral administration for 14 days starting from the 3rd week. The cardiopulmonary function, right ventricular pressure, cough and asthma index, lung injury, cell apoptosis, oxidative stress-related indicators, immune cells, and phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)/hypoxic inducible factor 1α(HIF-1α) pathway-related proteins or mRNA levels were examined. Furthermore, hypoxia-induced pulmonary arterial smooth muscle cell(PASMC) were used to further explore the mechanism of Phe intervention in PH combined with PI3K ago-nist(740Y-P). The results showed that Phe significantly improved the cardiopulmonary function of mice with PH, decreased right ventricular pressure, cough and asthma index, and lung injury, reduced cell apoptosis, oxidative stress-related indicators, and nuclear levels of phosphorylated Akt(p-Akt) and phosphorylated mTOR(p-mTOR), inhibited the expression levels of HIF-1α and PI3K mRNA and proteins, and maintained the immune cell homeostasis in mice. Further mechanistic studies revealed that Phe significantly reduced the viability and migration ability of hypoxia-induced PASMC, decreased the expression of HIF-1α and PI3K proteins and nuc-lear levels of p-Akt and p-mTOR, and this effect was blocked by 740Y-P. Therefore, it is inferred that Phe may exert anti-PH effects by alleviating the imbalance of oxidative stress and apoptosis in lung tissues and regulating immune levels, and its mechanism may be related to the regulation of the PI3K/Akt/mTOR/HIF-1α pathway. This study is expected to provide drug references and research ideas for the treatment of PH.
Asunto(s)
Glucósidos , Hipertensión Pulmonar , Subunidad alfa del Factor 1 Inducible por Hipoxia , Hipoxia , Ratones Endogámicos C57BL , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Rehmannia , Serina-Treonina Quinasas TOR , Animales , Masculino , Serina-Treonina Quinasas TOR/metabolismo , Serina-Treonina Quinasas TOR/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Ratones , Hipertensión Pulmonar/tratamiento farmacológico , Hipertensión Pulmonar/fisiopatología , Hipertensión Pulmonar/metabolismo , Hipertensión Pulmonar/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Rehmannia/química , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Glucósidos/farmacología , Hipoxia/tratamiento farmacológico , Hipoxia/fisiopatología , Hipoxia/metabolismo , Transducción de Señal/efectos de los fármacos , Humanos , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/química , Apoptosis/efectos de los fármacosRESUMEN
BACKGROUND: Thyroid Cancer (TC) is an endocrine organ malignancy that has become more common in recent decades. Vernodalin (VN), a cytotoxic sesquiterpene, has been reported to exhibit anticancer properties against human breast and liver cancer cells. However, no study has explored the efficacy of VN with respect to its antiproliferative and apoptotic action on human Papillary Thyroid Cancer cells (PTC). OBJECTIVE: The study intended to examine the antitumor and antiproliferative effects of VN and the apoptosis mechanisms underlying its action on TPC-1 human PTC cells. METHODS: In this study, we examined the VN cell viability by MTT assay; performed ROS measurement by DCFH staining method, MMP identification by Rh-123 staining method, and apoptotic morphological assay by employing AO/EB and DAPI stain method, and further, p38 MAPK/ERK/JNK cell proliferation markers were determined by western blotting technique. RESULTS: The findings showed that VN could inhibit the growth of PTC cells by increasing intracellular ROS, damaging MMP, and stimulating apoptosis in a concentration-dependent manner. The study demonstrated how VN inhibited TPC-1 cell viability by causing ROS-induced cell death via the MAPK signaling pathway. CONCLUSION: VN may serve as an agonist to impact apoptosis in PTC cells. In human PTC, VN could play an effective role in chemotherapy. More studies pertaining to animal tumor models are needed to prove its anti-cancer effectiveness in vivo.
Asunto(s)
Apoptosis , Proliferación Celular , Sistema de Señalización de MAP Quinasas , Especies Reactivas de Oxígeno , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides , Humanos , Apoptosis/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Cáncer Papilar Tiroideo/tratamiento farmacológico , Cáncer Papilar Tiroideo/patología , Cáncer Papilar Tiroideo/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Neoplasias de la Tiroides/tratamiento farmacológico , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/metabolismo , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Antineoplásicos/farmacología , Antineoplásicos/química , Sesquiterpenos/farmacología , Sesquiterpenos/química , Ensayos de Selección de Medicamentos Antitumorales , Línea Celular Tumoral , Relación Dosis-Respuesta a DrogaRESUMEN
The compound Honokiol, derived from the bark of Magnolia officinalis, possesses the ability to induce apoptosis and inhibit cellular damage caused by reactive oxygen species. The objective of this study was to investigate the toxicological and histopathological effects of Honokiol on zebrafish (Danio rerio) through conducting a semistatic acute toxicity test involving immersion in an Honokiol-containing solution. The results showed that the toxic effects of Honokiol on zebrafish were primarily manifested in the liver and gills. When exposed to 0.6 mg/L of Honokiol, it could lead to liver hemorrhage as well as swelling and necrosis of gill tissues, and high concentrations of Honokiol could trigger inflammatory responses. Additionally, research found that Honokiol could induce apoptosis in liver and gill tissues through the P53 pathway and possessed the ability to enhance antioxidation. The present findings significantly contribute to a more profound understanding of the toxic impact of Honokiol and its underlying mechanism, thereby providing a valuable reference for the future safe utilization of Honokiol and related pharmaceutical advancements.
Asunto(s)
Apoptosis , Compuestos de Bifenilo , Lignanos , Hígado , Pez Cebra , Lignanos/farmacología , Lignanos/toxicidad , Animales , Compuestos de Bifenilo/toxicidad , Hígado/efectos de los fármacos , Hígado/patología , Apoptosis/efectos de los fármacos , Branquias/efectos de los fármacos , Branquias/patología , Proteína p53 Supresora de Tumor/metabolismo , Magnolia/química , Compuestos Alílicos , FenolesRESUMEN
Here, the protective effect of antioxidant Idebenone (IDB) on renovascular hypertension was studied. The two-kidney one-clip (2K-1C) model of renal hypertension was established. The rats were divided into 3 groups: sham-operation group, 2K-1C renal hypertensive rats' model group and model treated with IDB group. The mean arterial blood pressure (MBP) of rats was measured and pathological condition of kidney was observed by H&E staining. The change of renal damage biomarkers (Cre, BUN, urine proteins), inflammatory factors (IL-6, IL-1ß and TNF-α), oxidative stress ratio and key factors (MDA, SOD and CAT) were assessed by kits. The apoptosis key proteins (BAD, BAX, Caspase9, GSK-3ß) were detected via Western blot. The 2K-1C model of renal hypertension was established. IDB reduced the MBP, Cre, BUN, urine proteins and improved the pathological condition of 2K-1C kidney. IDB restrained the inflammation factors (IL-6, IL-1ß and TNF-α) and oxidative stress in kidney of renal hypertensive rats' model. Besides, IDB suppressed the expression of apoptosis key factors (BAD, BAX, Caspase9, GSK-3ß) in kidney of renal hypertensive rats' model. IDB protects the kidneys of rats with renovascular arterial hypertension by inhibiting inflammation, oxidative stress, and apoptosis. These findings might provide medication guidance for IDB in renovascular arterial hypertension.
Asunto(s)
Apoptosis , Hipertensión Renovascular , Riñón , Estrés Oxidativo , Ubiquinona , Animales , Estrés Oxidativo/efectos de los fármacos , Hipertensión Renovascular/tratamiento farmacológico , Hipertensión Renovascular/metabolismo , Apoptosis/efectos de los fármacos , Riñón/efectos de los fármacos , Riñón/patología , Riñón/metabolismo , Masculino , Ubiquinona/análogos & derivados , Ubiquinona/farmacología , Ubiquinona/uso terapéutico , Ratas , Ratas Sprague-Dawley , Presión Sanguínea/efectos de los fármacos , Antioxidantes/farmacología , Modelos Animales de Enfermedad , Sustancias Protectoras/farmacologíaRESUMEN
OBJECTIVE: To investigate the cerebroprotective effects of leptin in vitro and in vivo via the Janus kinase-2 (JAK2)/transcription factor signal transducer and activators of transcription-3 (STAT3) pathway and leptin receptors (LEPR). METHODS: The study used the cellular oxygen-glucose deprivation (OGD) model in PC12 cells and the middle cerebral artery occlusion (MCAO) rat model of cerebral ischaemia-reperfusion injury (CIRI) to assess changes in gene expression and protein levels following leptin pretreatment. The methylated DNA immunoprecipitation (MeDIP) assay measured DNA methylation levels. RESULTS: The optimal leptin concentration for exerting neuroprotective effects against ischaemia-reperfusion injury in PC12 cells was 200 ng/ml in vitro, but excessive leptin diminished this effect. Leptin pretreatment in the MCAO rat model demonstrated a similar effect to previously reported leptin administration post-CIRI. In addition to regulating the expression of inflammation-related cytokines, Western blot analysis showed that leptin pretreatment upregulated BCL-2 and downregulated caspase 3 levels. The MeDIP analysis demonstrated that DNA methylation regulated LEPR gene expression in the MCAO rat model when leptin pretreatment was used. CONCLUSION: Exogenous leptin might bind to extra-activated LEPR by reducing the methylation level of the LEPR gene promoter region, which leads to an increase in phosphorylated JAK2/STAT3 and apoptotic signalling pathways.
Asunto(s)
Metilación de ADN , Janus Quinasa 2 , Leptina , Ratas Sprague-Dawley , Receptores de Leptina , Daño por Reperfusión , Factor de Transcripción STAT3 , Transducción de Señal , Animales , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patología , Janus Quinasa 2/metabolismo , Ratas , Factor de Transcripción STAT3/metabolismo , Transducción de Señal/efectos de los fármacos , Receptores de Leptina/metabolismo , Receptores de Leptina/genética , Masculino , Leptina/metabolismo , Células PC12 , Infarto de la Arteria Cerebral Media/metabolismo , Infarto de la Arteria Cerebral Media/patología , Modelos Animales de Enfermedad , Fármacos Neuroprotectores/farmacología , Apoptosis/efectos de los fármacos , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patología , Caspasa 3/metabolismoRESUMEN
Reactive oxygen species (ROS) are highly reactive oxygen-containing molecules generated as natural byproducts during cellular processes, including metabolism. Under normal conditions, ROS play crucial roles in diverse cellular functions, including cell signaling and immune responses. However, a disturbance in the balance between ROS production and cellular antioxidant defenses can lead to an excessive ROS buildup, causing oxidative stress. This stress damages essential cellular components, including lipids, proteins, and DNA, potentially culminating in oxidative cell death. This form of cell death can take various forms, such as ferroptosis, apoptosis, necroptosis, pyroptosis, paraptosis, parthanatos, and oxeiptosis, each displaying distinct genetic, biochemical, and signaling characteristics. The investigation of oxidative cell death holds promise for the development of pharmacological agents that are used to prevent tumorigenesis or treat established cancer. Specifically, targeting key antioxidant proteins, such as SLC7A11, GCLC, GPX4, TXN, and TXNRD, represents an emerging approach for inducing oxidative cell death in cancer cells. This review provides a comprehensive summary of recent progress, opportunities, and challenges in targeting oxidative cell death for cancer therapy.
Asunto(s)
Muerte Celular , Neoplasias , Estrés Oxidativo , Especies Reactivas de Oxígeno , Humanos , Neoplasias/metabolismo , Neoplasias/patología , Especies Reactivas de Oxígeno/metabolismo , Animales , Oxidación-Reducción , Antioxidantes/metabolismo , Antioxidantes/farmacología , Transducción de Señal , Apoptosis , Ferroptosis/efectos de los fármacosRESUMEN
BACKGROUND: Osteosarcoma (OS) is one of the most common primary malignant tumors of bone in children, which develops from osteoblasts and typically occurs during the rapid growth phase of the bone. Recently, Super-Enhancers(SEs)have been reported to play a crucial role in osteosarcoma growth and metastasis. Therefore, there is an urgent need to identify specific targeted inhibitors of SEs to assist clinical therapy. This study aimed to elucidate the role of BRD4 inhibitor GNE-987 targeting SEs in OS and preliminarily explore its mechanism. METHODS: We evaluated changes in osteosarcoma cells following treatment with a BRD4 inhibitor GNE-987. We assessed the anti-tumor effect of GNE-987 in vitro and in vivo by Western blot, CCK8, flow cytometry detection, clone formation, xenograft tumor size measurements, and Ki67 immunohistochemical staining, and combined ChIP-seq with RNA-seq techniques to find its anti-tumor mechanism. RESULTS: In this study, we found that extremely low concentrations of GNE-987(2-10 nM) significantly reduced the proliferation and survival of OS cells by degrading BRD4. In addition, we found that GNE-987 markedly induced cell cycle arrest and apoptosis in OS cells. Further study indicated that VHL was critical for GNE-987 to exert its antitumor effect in OS cells. Consistent with in vitro results, GNE-987 administration significantly reduced tumor size in xenograft models with minimal toxicity, and partially degraded the BRD4 protein. KRT80 was identified through analysis of the RNA-seq and ChIP-seq data. U2OS HiC analysis suggested a higher frequency of chromatin interactions near the KRT80 binding site. The enrichment of H3K27ac modification at KRT80 was significantly reduced after GNE-987 treatment. KRT80 was identified as playing an important role in OS occurrence and development. CONCLUSIONS: This research revealed that GNE-987 selectively degraded BRD4 and disrupted the transcriptional regulation of oncogenes in OS. GNE-987 has the potential to affect KRT80 against OS.
Asunto(s)
Apoptosis , Neoplasias Óseas , Proteínas de Ciclo Celular , Proliferación Celular , Osteosarcoma , Factores de Transcripción , Animales , Humanos , Ratones , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Apoptosis/efectos de los fármacos , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/patología , Neoplasias Óseas/genética , Neoplasias Óseas/metabolismo , Proteínas que Contienen Bromodominio , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/antagonistas & inhibidores , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Elementos de Facilitación Genéticos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Ratones Desnudos , Osteosarcoma/tratamiento farmacológico , Osteosarcoma/patología , Osteosarcoma/genética , Osteosarcoma/metabolismo , Factores de Transcripción/metabolismo , Factores de Transcripción/antagonistas & inhibidores , Factores de Transcripción/genética , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Sevoflurane (Sev) is a commonly used inhalation anaesthetic that has been shown to cause hippocampus dysfunction through multiple underlying molecular processes, including mitochondrial malfunction, oxidative stress and inflammation. Dihydromyricetin (DHM) is a 2,3-dihydroflavonoid with various biological properties, such as anti-inflammation and anti-oxidative stress. The purpose of this study was to investigate the effect of DHM on Sev-induced neuronal dysfunction. HT22 cells were incubated with 10, 20 and 30 µM of DHM for 24 h, and then stimulated with 4% Sev for 6 h. The effects and mechanism of DHM on inflammation, oxidative stress and mitochondrial dysfunction were explored in Sev-induced HT22 cells by Cell Counting Kit-8, flow cytometry, enzyme-linked immunosorbent assay, reverse transcription-quantitative polymerase chain reaction, colorimetric detections, detection of the level of reactive oxygen species (ROS), mitochondrial ROS and mitochondrial membrane potential (MMP), immunofluorescence and western blotting. Our results showed that DHM increased Sev-induced cell viability of HT22 cells. Pretreatment with DHM attenuated apoptosis, inflammation, oxidative stress and mitochondrial dysfunction in Sev-elicited HT22 cells by remedying the abnormality of the indicators involved in these progresses, including apoptosis rate, the cleaved-caspase 3 expression, as well as the level of tumour necrosis factor α, interleukin (IL)-1ß, IL-6, malondialdehyde, superoxide dismutase, catalase, ROS, mitochondrial ROS and MMP. Mechanically, pretreatment with DHM restored the Sev-induced the expression of SIRT1/FOXO3a pathway in HT22 cells. Blocking of SIRT1 counteracted the mitigatory effect of DHM on apoptosis, inflammation, oxidative stress and mitochondrial dysfunction in Sev-elicited HT22 cells. Collectively, pretreatment with DHM improved inflammation, oxidative stress and mitochondrial dysfunction via SIRT1/FOXO3a pathway in Sev-induced HT22 cells.
Asunto(s)
Apoptosis , Flavonoles , Hipocampo , Mitocondrias , Estrés Oxidativo , Sevoflurano , Flavonoles/farmacología , Animales , Ratones , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Hipocampo/citología , Hipocampo/patología , Línea Celular , Sevoflurano/farmacología , Estrés Oxidativo/efectos de los fármacos , Apoptosis/efectos de los fármacos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Supervivencia Celular/efectos de los fármacos , Sirtuina 1/metabolismo , Fármacos Neuroprotectores/farmacologíaAsunto(s)
Carcinoma de Células Renales , Transición Epitelial-Mesenquimal , Neoplasias Renales , Metiltransferasas , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/patología , Humanos , Neoplasias Renales/genética , Neoplasias Renales/patología , Neoplasias Renales/metabolismo , Metiltransferasas/metabolismo , Metiltransferasas/genética , Metilación , Adenosina/análogos & derivados , Adenosina/metabolismo , Epigénesis Genética , Resistencia a Antineoplásicos , Invasividad Neoplásica , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Pronóstico , Apoptosis , Regulación Neoplásica de la Expresión Génica , Factores de Empalme de ARN/genética , Factores de Empalme de ARN/metabolismoRESUMEN
PURPOSE: To investigate the inhibitory effect of sodium cantharidate (SCA) on human tongue squamous cell carcinoma CAL27 cells and its mechanism. METHODS: CAL27 cells were pretreated with different concentrations of SCA. Cell viability was analyzed by CCK-8 method. The migration and invasion of CAL27 cells were measured by scratch test and Transwell chamber, and the apoptosis rate was measured by flow cytometry. p53 protein and its phosphorylation sites Ser33, Ser37, Ser46, expression of BCL-2, BAX, and cleaved caspase 3 in CAL27 cells were detected by Western blot. Statistical analysis was performed with Graphpad Prism 9.0 software package. RESULTS: Compared with the blank control group, the proliferation, migration and invasion of CAL27 cells in sodium cantharidate group were significantly decreased, and the apoptosis rate was significantly increased(Pï¼0.01) in a dose-dependent manner. The expression of p53 protein and its phosphorylation sites Ser33, Ser37, Ser46 protein was significantly up-regulated(Pï¼0.05 or Pï¼0.01). The expression of BCL-2 protein was down-regulated and the expression of BAX protein was significantly up-regulated(Pï¼0.05 or Pï¼0.01). The ratio of BCL-2/BAX was significantly decreased and the expression of cleaved caspase 3 protein was significantly up-regulated(Pï¼0.05 or Pï¼0.01). CONCLUSIONS: SCA can inhibit the proliferation, migration and invasion of human tongue squamous cell carcinoma CAL27 cells. It also down-regulates the ratio of BCL-2/BAX and up-regulates the expression of cleaved caspase 3 protein by regulating the phosphorylation of p53 protein, which induces apoptosis.
Asunto(s)
Apoptosis , Carcinoma de Células Escamosas , Movimiento Celular , Proliferación Celular , Neoplasias de la Lengua , Proteína p53 Supresora de Tumor , Proteína X Asociada a bcl-2 , Humanos , Neoplasias de la Lengua/tratamiento farmacológico , Neoplasias de la Lengua/metabolismo , Neoplasias de la Lengua/genética , Carcinoma de Células Escamosas/metabolismo , Línea Celular Tumoral , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Proteína p53 Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/genética , Fosforilación/efectos de los fármacos , Proteína X Asociada a bcl-2/metabolismo , Proteína X Asociada a bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/genética , Caspasa 3/metabolismo , Supervivencia Celular/efectos de los fármacos , Invasividad NeoplásicaRESUMEN
Long non-coding ribose nucleic acids (lncRNAs) have been implicated in the development of nephrolithiasis. The study aims to investigate the interplay of lncRNA SBF2-AS1 (SETbinding factor 2 antisense RNA 1) and NLR family pyrin domain containing 3 (NLRP3) in regulating the calcium oxalate monohydrate (COM)-induced human kidney HK-2 cell injury. HK-2 cells were treated with COM (100 µg/mL) to create a cellular model of kidney injury. Gene and protein expression was assessed by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and Western blot. Proliferation and apoptosis rates, as well as levels of malondialdehyde (MDA), lactate dehydrogenase (LDH), superoxide dismutase (SOD), tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 were measured. Additionally, potential miRNAs interacting with SBF2-AS1 and NLRP3 were predicted utilizing the starBase and TargetScan databases. The interference of SBF2-AS1 resulted in increased cell proliferation and SOD levels in HK-2 cells after COM induction. SBF2-AS1 silencing also reduced COM-induced cell death and inflammatory cytokine production by down-regulating NLRP3 protein expression. Conversely, forced upregulation of NLRP3 abrogated the effect of SBF2-AS1 interference. Notably, SBF2-AS1 interference on COM-induced oxidative stress and COM-induced cellular damage was rescued by antioxidant, indicating the involvement of oxidative burden in COM-induced damage. miR-302e acted as a mediator miRNA linking the functional association of SBF2-AS1 and NLRP3. Silencing SBF2-AS1 promoted miR-302e level and miR-302e reduced NLRP3 expression in HK-2 cells to protect against COM-induced damage. In summary, these findings suggest that downregulation of lncRNA SBF2-AS1 can potentially protect HK-2 cells from COM-induced injury by modulating the miR-302e/NLRP3 pathway.