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1.
Food Chem ; 367: 130767, 2022 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-34391996

RESUMEN

This study aimed to investigate the effect of caspase-3 inhibitor in mitochondrial apoptosis activation on structure protein degradation during postmortem storage. Mitochondrial dysfunction, apoptotic factors, structure protein degradation and the myofibrillar rupture index between the control and caspase-3 inhibitor groups were determined. The results show caspase-3 inhibitor repressed the mitochondrial membrane permeability and mitochondrial swelling, as well as increased mitochondrial membrane potential, causing a decrease in the release of cytochrome c from mitochondria to cytoplasm and caspase-9/3 activities (P < 0.05). Subsequently, small myofibrillar proteins (desmin and troponin-T) were susceptible to degradation, initiating texture deterioration. By contrast, giant structure proteins (titin and nebulin) were degraded during later postmortem storage, predominantly contributing to fish softening. The results further suggest that caspase-3 is involved in degradation of structure proteins during postmortem through mitochondrial apoptosis pathways.


Asunto(s)
Esocidae , Mitocondrias , Animales , Apoptosis , Caspasa 3/genética , Caspasa 3/metabolismo , Caspasa 9/metabolismo , Esocidae/metabolismo , Mitocondrias/metabolismo , Membranas Mitocondriales/metabolismo
2.
Talanta ; 236: 122899, 2022 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-34635272

RESUMEN

A real-time quartz crystal microbalance (QCM) cytosensor was first developed for dynamical and noninvasive monitoring of cell viscoelasticity for evaluation of apoptosis degree. In this work, human breast cancer cells MCF-7 and MDA-MB-231 were employed as cell model and respectively captured on the surface of QCM electrode modified with mercaptosuccinic acid and poly-l-lysine. Cell viscoelasticity was measured dynamically by real-time monitoring energy dissipation with QCM, and the dynamic diagram of the energy dissipation of MDA-MB-231 cells treated with curcumin was first obtained. The results displayed that the changes of energy dissipation in MDA-MB-231 cells and MCF-7 cells were 8.81 × 10-6 and 5.29 × 10-6, particularly due to the difference in cell viscoelasticity. Furthermore, curcumin was used to induce cell apoptosis and suppress energy dissipation of MDA-MB-231 cells. Combining apoptosis assay with QCM measurement, the results revealed good linear relationship between cell viscoelasticity inhibition and apoptosis rate with correlation coefficient R = 0.9908. The QCM cytosensor could rapidly, accurately, dynamically, and noninvasively monitor the changes of cell viscoelasticity for evaluation of apoptosis degree in MDA-MB-231 cells. The study established a new model for cell apoptosis assessment, facilitating understanding of the mechanisms of cell apoptosis on the aspect of mechanical properties.


Asunto(s)
Técnicas Biosensibles , Neoplasias de la Mama , Curcumina , Apoptosis , Neoplasias de la Mama/tratamiento farmacológico , Curcumina/farmacología , Femenino , Humanos , Viscosidad
3.
Food Chem ; 368: 130816, 2022 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-34416489

RESUMEN

Acrylamide (AA), a potential carcinogen, is commonly formed in foods rich in carbohydrates at high heat. It is known that AA-induced mitochondrial dysfunction is responsible for its toxicity. Previously we found AA exposure increased miR-27a-5p expression in livers of SD rats. Here, the regulation mechanism of miR-27a-5p in mitochondrial dysfunction was investigated in rat liver cell lines (IAR20) and SD rats. The results showed that the overexpressed miR-27a-5p contributes to modulating mitochondrial dysfunction and Btf3 is identified as its target gene. The knockdown of Btf3 increases the cleaved PARP1 level and the phosphorylation of ATM and p53, which results in mitochondria-dependent apoptosis. Therefore, the miR-27a-5p-Btf3-ATM-p53 axis might play a vital role in the promotion of AA-induced cell apoptosis through disrupting mitochondrial structure and function. This would provide a potential target for the assessment and intervention of AA toxicity.


Asunto(s)
MicroARNs , Acrilamida/toxicidad , Animales , Apoptosis , MicroARNs/genética , Mitocondrias/genética , Ratas , Ratas Sprague-Dawley
4.
Chaos ; 31(9): 093103, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34598451

RESUMEN

The crosstalk between pyroptosis and apoptosis pathways plays crucial roles in homeostasis, cancer, and other pathologies. However, its molecular regulatory mechanisms for cell death decision-making remain to be elucidated. Based on the recent experimental studies, we developed a core regulatory network model of the crosstalk between pyroptosis and apoptosis pathways. Sensitivity analysis and bifurcation analysis were performed to assess the death mode switching of the network. Both the approaches determined that only the level of caspase-1 or gasdermin D (GSDMD) has the potential to individually change death modes. The decrease of caspase-1 or GSDMD switches cell death from pyroptosis to apoptosis. Seven biochemical reactions among the 21 reactions in total that are essential for determining cell death modes are identified by using sensitivity analysis. While with bifurcation analysis of state transitions, nine reactions are suggested to be able to efficiently switch death modes. Monostability, bistability, and tristability are observed under different conditions. We found that only the reaction that caspase-1 activation induced by stimuli can trigger tristability. Six and two of the nine reactions are identified to be able to induce bistability and monostability, respectively. Moreover, the concurrence of pyroptosis and apoptosis is observed not only within proper bistable ranges, but also within tristable ranges, implying two potentially distinct regulatory mechanisms. Taken together, this work sheds new light on the crosstalk between pyroptosis and apoptosis and uncovers the regulatory mechanisms of various stable state transitions, which play important roles for the development of potential control strategies for disease prevention and treatment.


Asunto(s)
Inflamasomas , Péptidos y Proteínas de Señalización Intracelular , Apoptosis , Muerte Celular , Inflamasomas/metabolismo , Proteínas de Unión a Fosfato
5.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 39(5): 540-546, 2021 Oct 01.
Artículo en Inglés, Chino | MEDLINE | ID: mdl-34636201

RESUMEN

OBJECTIVES: This study aims to explore the effect of acidic culture conditions on the proliferation, apoptosis, and migration ability of human tongue squamous cell carcinoma SCC15 and CAL27 cells and its potential molecular mechanism. METHODS: After acidic culture for different periods, methyl thiazolyl tetrazolium (MTT) method was adop-ted to detect the cell proliferation of SCC15 and CAL27. Flow cytometry was employed to detect the apoptosis level of SCC15 and CAL27 cells. The migration ability of SCC15 and CAL27 after acidic culture was detected by scratch hea-ling test. Real-time fluorescence quantitative polymerase chain reaction (FQ-PCR) was used to detect the mRNA expression of cyclooxygenase 2 (COX-2) and survivin in SCC15 and CAL27 cells after acidic culture. RESULTS: After culture for 24 h under acidic microenvironment, SCC15 and CAL27 cells grew rapidly and reached the stationary phase after adjustment for 3 days. The apoptosis levels of SCC15 and CAL27 cells decreased after acidic culture, but the most significant reduction occurred after 6 h of acidic culture. The scratch healing rates of SCC15 and CAL27 cells increased after acidic culture. The results of FQ-PCR showed that the mRNA expression levels of COX-2 and survivin in SCC15 and CAL27 cells increased after acidic culture. CONCLUSIONS: Extracellular acidic microenvironment can inhibit the apoptosis of tongue squamous carcinoma cells, promote their migration, and induce more adaptable and malignant tongue squamous carcinoma cells. The mechanism may be related to COX-2 and survivin and their signal pathways.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de la Boca , Neoplasias de la Lengua , Apoptosis , Línea Celular Tumoral , Proliferación Celular , Humanos , Lengua , Microambiente Tumoral
6.
BMC Cancer ; 21(1): 1069, 2021 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-34592939

RESUMEN

BACKGROUND: Colorectal cancer (CRC) represents one of the major malignant cancers in the world. It has been demonstrated that long non-coding RNAs (lncRNAs) can cause great influences on various human cancers. Though MCF.2 cell line derived transforming sequence like antisense RNA 1 (MCF2L-AS1) and its carcinogenic effect in CRC has been elucidated by several previous researches, the underlying mechanism remains unknown. AIM: We aimed at exploring the function and regulatory mechanism of MCF2L-AS1 in CRC. METHODS: MCF2L-AS1 expression in CRC cells was tested via RT-qPCR assay. The effects of MCF2L-AS1 on the biological properties of CRC cells were testified through functional experiments. The molecular mechanism of MCF2L-AS1 was verified through mechanism experiments. RESULTS: MCF2L-AS1 was highly expressed in CRC cells, and it could enhance the proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) process of CRC cells. MiR-105-5p was sponged by MCF2L-AS1 in CRC cells and Ras-related protein Rab-22A (RAB22A) was verified to be the downstream target of miR-105-5p. It was verified through rescue assays that RAB22A overexpression or miR-105-5p silencing could reverse the repressive impact of MCF2L-AS1 silencing on CRC progression. CONCLUSION: MCF2L-AS1 accelerated the malignant development of CRC cells by targeting the miR-105-5p/RAB22A axis.


Asunto(s)
Neoplasias Colorrectales/metabolismo , MicroARNs/metabolismo , Proteínas de Neoplasias/metabolismo , Factores de Intercambio de Guanina Nucleótido Rho/metabolismo , Proteínas de Unión al GTP rab/metabolismo , Apoptosis , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Neoplasias Colorrectales/patología , Progresión de la Enfermedad , Transición Epitelial-Mesenquimal , Silenciador del Gen , Humanos , MicroARNs/genética , Invasividad Neoplásica
7.
Anticancer Res ; 41(10): 4885-4894, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34593436

RESUMEN

BACKGROUND/AIM: Advanced undifferentiated pleomorphic sarcoma (UPS) has a poor prognosis and there are few treatments that can improve overall survival. Recently, Rapalink-1, a third-generation mammalian target of rapamycin (mTOR) kinase inhibitor, has been developed and shown to be effective against other tumours. However, mTOR inhibitors have been shown to induce autophagy and resistance to anti-cancer drugs. This study aimed to investigate the antitumor effects of Rapalink-1 with an autophagy inhibitor. MATERIALS AND METHODS: The antitumor effect of Rapalink-1 and/or hydroxychloroquine in three UPS cell lines was examined via cell viability analysis, western blotting, flow cytometry and immunofluorescence. RESULTS: Rapalink-1 decreased cell proliferation and inhibited the PI3K/mTOR pathway. Combined treatment with Rapalink-1 and hydroxychloroquine enhanced the antitumor effect compared to treatment with Rapalink-1 alone by blocking the autophagy-inducing effect of mTOR inhibitors. CONCLUSION: Combined treatment with Rapalink-1 and hydroxychloroquine may be used as a potential therapeutic agent against UPS.


Asunto(s)
Apoptosis , Autofagia , Hidroxicloroquina/farmacología , Sarcoma/patología , Sirolimus/análogos & derivados , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Proliferación Celular , Inhibidores Enzimáticos/farmacología , Humanos , Sarcoma/tratamiento farmacológico , Sarcoma/metabolismo , Sirolimus/farmacología , Células Tumorales Cultivadas
8.
Anticancer Res ; 41(10): 4907-4916, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34593438

RESUMEN

BACKGROUND: Interleukin-6 receptor antibody (IL6R) inhibits colony formation and invasion by colorectal carcinoma (CRC) in vitro. We examined the effect of IL6R antibody on tumor growth of CRC xenografts in vivo. MATERIALS AND METHODS: SW480 cells inoculated subcutaneously into NU/NU mice were treated with anti-IL6R and tumor histology and growth-related signaling were subsequently estimated by hematoxylin and eosin and immunohistochemical staining. RESULTS: Tumor growth was inhibited by anti-IL6R treatment at dosages of both 0.1 and 1.0 mg/kg. Tumor cells had invaded into surrounding tissues in untreated mice, while there was no invasion of tumors in the IL6R antibody-treated mice. The expression of Ki-67, signal transducer and activator of transcription protein 3 (STAT3) and phosphor-extracellular signal-regulated kinase 1 and 2 (ERK1/2) were suppressed in anti-IL6R-treated tumors. CONCLUSION: IL6R antibody inhibited tumor growth and invasiveness in vivo by suppressing the expression of Ki-67, STAT3 and phosphor-ERK1/2. The results imply that the anti-IL6R may be a promising targeted drug for CRC.


Asunto(s)
Anticuerpos Monoclonales/farmacología , Neoplasias Colorrectales/prevención & control , Neovascularización Patológica/prevención & control , Receptores de Interleucina-6/antagonistas & inhibidores , Animales , Apoptosis , Proliferación Celular , Neoplasias Colorrectales/inmunología , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Humanos , Masculino , Ratones , Ratones Desnudos , Neovascularización Patológica/inmunología , Neovascularización Patológica/metabolismo , Neovascularización Patológica/patología , Receptores de Interleucina-6/inmunología , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismo , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto
9.
Anticancer Res ; 41(10): 4917-4928, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34593439

RESUMEN

BACKGROUND/AIM: The functions of interleukin 33 (IL-33) in cholangiocarcinoma (CCA) are unclear. This study aimed to evaluate the roles of IL-33 in CCA progression. MATERIALS AND METHODS: The effect of intracellular IL-33 using shIL-33 knocked down KKU-055 (IL-33KD-KKU-055) compared to parental (Pa) KKU-055 and extracellular IL-33 using recombinant human IL-33 (rhIL-33) treatment on the proliferation and invasion of CCA cells grown in 3D cultures was studied. Relevant markers were determined by western blot or ELISA. RESULTS: IL-33KD-KKU-055 cells showed increased proliferation and invasion in 3D cultures compared to Pa-KKU-055 cells, with NF-κB and IL-6 up-regulation. Treatment with 2 ng/ml rhIL-33 promoted Pa-KKU-055 cell proliferation by inducing NF-κB and IL-6 expressions. Upon GSK-3ß inactivation and increased nuclear full-length IL-33 (flIL-33), 20 ng/ml rhIL-33 had no effect on proliferation. Both 2 and 20 ng/ml rhIL-33 induced proliferation and invasion of IL-33-negative KKU-213 cells in 3D cultures, as well as NF-κB and IL-6 up-regulation. CONCLUSION: Intracellular and extracellular IL-33 have distinct roles in the mechanisms of CCA progression.


Asunto(s)
Neoplasias de los Conductos Biliares/prevención & control , Biomarcadores de Tumor/metabolismo , Colangiocarcinoma/prevención & control , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Interleucina-33/farmacología , FN-kappa B/metabolismo , Apoptosis , Neoplasias de los Conductos Biliares/metabolismo , Neoplasias de los Conductos Biliares/patología , Biomarcadores de Tumor/genética , Proliferación Celular , Colangiocarcinoma/metabolismo , Colangiocarcinoma/patología , Glucógeno Sintasa Quinasa 3 beta/genética , Humanos , FN-kappa B/genética , Invasividad Neoplásica , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto
10.
Anticancer Res ; 41(10): 4929-4936, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34593440

RESUMEN

BACKGROUND/AIM: A new set of LQB-nitrones and analogues was synthesized to evaluate anticancer activity based on the substitution of the terpenyl moiety of the antileukemic compound LQB-278 by the conformationally restricted cinnamyl ether. MATERIALS AND METHODS: A structure-activity relationship study was performed in vitro on Jurkat cells to screen the antileukemic activity of LQB-nitrones and analogues and elucidate the mechanisms of action of the most active derivatives. RESULTS: The cynamyl ramification and its ortho position aldehyde substitution improved the antileukemic activity. Three compounds showed an in vitro antiproliferative action, but only 5b induced apoptosis. Analysis of the molecular mechanisms showed increased expression of the cell cycle inhibitor p21CIP1/WAF1/Sdi1, caspase 3, Fas receptor, and Bax/Bcl-2 ratio. CONCLUSION: The cinnamyl derivative 5b (LQB-461) presented higher antileukemic effects than the prototype terpenyl nitrone, inducing Jurkat cell death by activating both extrinsic and intrinsic pathways of apoptosis. Therefore, this compound is a new promising candidate drug against leukemia.


Asunto(s)
Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Leucemia/tratamiento farmacológico , Óxidos de Nitrógeno/química , Óxidos de Nitrógeno/farmacología , Apoptosis , Proliferación Celular , Humanos , Leucemia/patología , Células Tumorales Cultivadas
11.
Anticancer Res ; 41(10): 4937-4946, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34593441

RESUMEN

BACKGROUND/AIM: Dysregulation of the c-Myc gene is frequently found in human hepatocellular carcinoma (HCC), often accompanied by genetic and epigenetic alterations in other cancer-related genes. Here, we investigated the tumorigenic potential of c-Myc in diverse genetic environments in which the Ras, Wnt/ß-catenin, Sonic hedgehog, or P53 pathways were either activated or inactivated. MATERIALS AND METHODS: Hydrodynamic tail vein injection was employed to administer expression transposons and generate transgenic livers expressing c-Myc together with a constitutively active form of RAS (HRASG12V), ß-catenin (ß-cateninS33Y), Smo (SmoM2), or short hairpin RNA targeting P53 (shp53). RESULTS: c-Myc was most tumorigenic when the RAS signaling pathway was activated, whereas no tumors were found in mice when either ß-cateninS33Y or SmoM2 was co-expressed with c-Myc. Approximately 40% of mice had HCC when c-Myc was over-expressed under P53 inactivation. Furthermore, we investigated the effect of mutation in c-Myc on hepatocarcinogenesis. CONCLUSION: No significant differences in tumorigenic potential were found between wild type c-Myc and c-MycT58A, minimizing the role of the mutation in hepatocarcinogenesis.


Asunto(s)
Carcinogénesis/patología , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas Experimentales/patología , Neoplasias Hepáticas/patología , Proteínas Proto-Oncogénicas c-myc/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Animales , Apoptosis , Carcinogénesis/genética , Carcinogénesis/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Proliferación Celular , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas Experimentales/genética , Neoplasias Hepáticas Experimentales/metabolismo , Ratones , Ratones Endogámicos C57BL , Proteínas Proto-Oncogénicas c-myc/genética , Células Tumorales Cultivadas , Proteína p53 Supresora de Tumor/genética
12.
Anticancer Res ; 41(10): 4947-4955, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34593442

RESUMEN

BACKGROUND/AIM: Auranofin (AUR), a thioredoxin reductase (TXNRD) inhibitor, shows anticancer activity against several cancers. This study investigated the effects of AUR on the local progression and pulmonary metastasis of osteosarcoma (OS). MATERIALS AND METHODS: Publicly available expression cohorts were analysed to study the relationship between TXNRD-2 expression and the survival of patients with OS. The murine OS cell line LM8 was stimulated with AUR. Cell viability, apoptosis-related protein levels, caspase activity, and wound healing were analysed. Tumor progression and pulmonary metastasis were investigated in C3H mice implanted with LM8 cells. RESULTS: High-level expression of TXNRD-2 represented a negative prognostic factor for metastasis and overall survival in patients with OS. AUR induced apoptosis of OS cells via the oxidative stress-MAPK-Caspase 3 pathway, and suppressed the migration of OS cells. AUR inhibited the pulmonary metastasis of OS, but not local progression. CONCLUSION: AUR represents a potential therapeutic drug for suppressing pulmonary metastasis of OS.


Asunto(s)
Auranofina/farmacología , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Osteosarcoma/tratamiento farmacológico , Reductasa de Tiorredoxina-Disulfuro/antagonistas & inhibidores , Animales , Antirreumáticos/farmacología , Apoptosis , Neoplasias Óseas/metabolismo , Neoplasias Óseas/patología , Movimiento Celular , Proliferación Celular , Femenino , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundario , Ratones , Ratones Endogámicos C3H , Osteosarcoma/metabolismo , Osteosarcoma/patología , Pronóstico , Tasa de Supervivencia , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto
13.
Anticancer Res ; 41(10): 4957-4968, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34593443

RESUMEN

BACKGROUND/AIM: Cancer stem cells (CSCs) have been suggested playing a crucial role in the tumorigenesis and tumor progression. Clinically, concurrent chemoradiotherapy (CCRT) after transurethral resection of the bladder is the widely accepted treatment option for high-grade bladder urothelial carcinoma (UC); however, a proportion of bladder UC patients still suffer from recurrence and metastasis. In the present study, we investigated the stemness properties of bladder UC cells with respect to various disease stages. The metastatic capability and epithelial-mesenchymal transition (EMT) of the parental cells and the CSC cells of bladder UC, after chemotherapy with cisplatin alone or CCRT were also studied, respectively. MATERIALS AND METHODS: The aldehyde dehydrogenase (ALDH)-positive cells were analyzed by a flow cytometer. The inhibitory effects of radiation in combination with cisplatin on the cell viability, migration, invasion and EMT characteristics were also examined. RESULTS: We found that the proportion of ALDH+-CSCs of bladder UC cells and the disease grading were independent. Furthermore, cisplatin alone significantly (p<0.05) enhanced the migration of both grade-III T24 cells and advanced-stage HT1197 cells, while CCRT treatment significantly (p<0.05) inhibited the T24 cell migration capability, compared to the cisplatin alone group. Interestingly, we found that the cell invasion capability was obviously increased upon the treatment with CCRT in both T24 and HT1197 CSCs. Furthermore, cisplatin played a promoting role in EMT whether in the presence or absence of irradiation. CONCLUSION: CSCs as well as EMT signaling might contribute to the resistance and metastasis of one-shot CCRT in malignant bladder cancer.


Asunto(s)
Quimioradioterapia/métodos , Resistencia a Antineoplásicos , Transición Epitelial-Mesenquimal , Neoplasias de la Vejiga Urinaria/terapia , Apoptosis , Proliferación Celular , Humanos , Metástasis de la Neoplasia , Células Tumorales Cultivadas , Neoplasias de la Vejiga Urinaria/patología
14.
Anticancer Res ; 41(10): 4969-4977, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34593444

RESUMEN

BACKGROUND/AIM: To identify the best of three isatin-based scaffolds in terms of anticancer activity. MATERIALS AND METHODS: Synthesis of isatin-based scaffolds was performed through a reaction to form Schiff bases. In silico analyses consisted of a target prediction with the Swiss Target Prediction tool and a molecular docking by AutoDock Vina. Anticancer activity and cytotoxicity were determined using the WST1 viability assay. RESULTS: Three scaffolds (IA, IB, and IC) were synthesized and confirmed with good reaction yields. The Swiss Target Prediction tool showed a trend towards kinases. Molecular docking assays demonstrated higher affinity of IC towards CDK2. Anticancer activity assays identified IC as the most active against the cancer cell lines. Cytotoxicity results in non-cancer cells suggested a lack of selectivity. CONCLUSION: The scaffold IC was identified as the best in terms of anticancer activity and these effects may be due to inhibition of CDK2, as evidenced by molecular docking.


Asunto(s)
Antineoplásicos/farmacología , Quinasa 2 Dependiente de la Ciclina/metabolismo , Isatina/farmacología , Simulación del Acoplamiento Molecular/métodos , Neoplasias/tratamiento farmacológico , Bases de Schiff/química , Antineoplásicos/química , Apoptosis , Proliferación Celular , Humanos , Isatina/química , Neoplasias/metabolismo , Neoplasias/patología , Relación Estructura-Actividad , Células Tumorales Cultivadas
15.
Folia Biol (Praha) ; 67(2): 49-61, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34624937

RESUMEN

This study investigated the impact of exogenous replacement therapy with acylated ghrelin (AG) post sleeve gastrectomy (SG) on the memory function in rats. In addition, we investigated the possible underlying mechanisms, including the effects on markers of oxidative stress, tau phosphorylation, and apoptosis. Adult male Wistar rats were divided into four groups (N = 18/group) as follows: sham (control), SG, SG+AG (100 µM), and SG+AG+LY294002 (0.25 µg/100 g). We continued all treatments daily for four weeks post-surgery. SG impaired the spatial, retention, and recognition memories as tested by the Morris water maze test, passive avoidance test, and novel object recognition test, respectively. Also, it enhanced the levels of reactive oxygen species and lipid peroxides, reduced glutathione and protein levels of Bcl-2, and increased the levels of Bax and cleaved caspase-3 in the hippocampus. In addition, SG reduced the hippocampal levels of acetylcholine and brain-derived neurotrophic factor. Concomitantly, it inhibited the hippocampal activity of Akt and increased the activity of glycogen synthase kinase 3ß and tau protein phosphorylation. Exogenous administration of acylated ghrelin to rats that had undergone SG prevented memory deficits. Also, it prevented the alteration in the above-mentioned biochemical parameters, an effect that was abolished by co-administration of LY294002 (phosphoinositide 3-kinase inhibitor). In conclusion, AG replacement therapy after SG in rats protects them against memory deficits and hippocampal damage by suppressing tau protein phosphorylation, mediated by activating PI3K/Aktinduced inhibition of glycogen synthase kinase 3ß.


Asunto(s)
Ghrelina , Proteínas tau , Animales , Apoptosis , Gastrectomía , Ghrelina/metabolismo , Ghrelina/farmacología , Hipocampo/metabolismo , Masculino , Estrés Oxidativo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Ratas Wistar , Proteínas tau/metabolismo
16.
Artículo en Chino | MEDLINE | ID: mdl-34624962

RESUMEN

Endocrine disrupting chemicals (EDCs) are a kind of exogenous chemicals widely existing in the environment, which cause serious harm to the environment and human health. At present, the impact of this type of substance on the thyroid has attracted much attention.This review summarized the effects of EDCs on thyroid hormones, and phosphatidylinositol 3-kinase (PI3K) /protein kinase B (Akt) /mammalian target of rapamycin (mTOR) (PI3K/Akt/mTOR) signaling pathway and its role in thyroid diseases, and explore the role of PI3K/Akt/mTOR signaling pathway in EDCs-induced apoptosis and autophagy of thyroid follicular epithelial cells.This paper could provide further understandings for thyroid diseases induced by the autophagy and apoptosis of thyroid follicular epithelial cells.


Asunto(s)
Disruptores Endocrinos , Células Epiteliales Tiroideas , Apoptosis , Autofagia , Disruptores Endocrinos/toxicidad , Humanos , Fosfatidilinositol 3-Quinasa/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo , Células Epiteliales Tiroideas/metabolismo
17.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(5): 1394-1402, 2021 Oct.
Artículo en Chino | MEDLINE | ID: mdl-34627416

RESUMEN

OBJECTIVE: To investigate the effect of glycolytic enzyme pyruvate kinase type 2 (PKM2) on the proliferation and apoptosis of human leukemia HL-60 cells. METHODS: si-PKM2 plasmid was transfected into HL-60 cells (set as si-PKM2 group), and blank vector transfected cells were set as control group (si-Ctl group). The expression levels of PKM2 mRNA and protein in si-Ctl group and si-PKM2 group were detected by RT-qPCR and Western blot. CCK-8 cell detection kit was used to detect the proliferation ability of the cells in the two groups. Flow cytometry was used to detect the changes of cell cycle and apoptosis. Western blot and RT-qPCR were used to detect the changes of p-Akt and p-mTOR protein levels in PI3K/Akt/mTOR signaling pathway and the changes of glycolysis-related mRNA levels of the cells in the two groups. The changes in glucose consumption and lactic acid production of the cells were assayed. Over expressed PKM2, HL-60 cells were treated with PI3K inhibitor LY294002 or galactose, the changes in cell proliferation ability, cell cycle and apoptosis, as well as changes in glucose consumption and lactic acid production were detected. RESULTS: Interfered by si-PKM2, mRNA and protein levels of PKM2 in si-PKM2 group significantly decreased, and proliferation ability of the cells was also reduced (P<0.05). After PKM2 knockdown, the cells were significantly blocked at G1 phase, and cell apoptosis was obviously induced (P<0.05). p-Akt and p-mTOR levels were lower in si-PKM2 group than those in si-Ctl group. The glucose consumption and lactic acid production significantly decreased in si-PKM2 cells. Overexpressed PKM2, HL-60 cells were treated with PI3K inhibitor LY294002. The glucose consumption and lactate acid production induced by overexpressed PKM2 were reduced. Overexpressed PKM2, HL-60 cells showed no significant changes in cell proliferation, cycle and apoptosis when cultured with galactose. CONCLUSION: PKM2 knockdown can inhibit the proliferation and induce apoptosis of HL-60 cells, and its molecular mechanism may be related to the PKM2-mediated PI3K/Akt/mTOR-glycolysis, which suggesting that PKM2 may serve as a molecular target for the prevention and treatment of leukemia.


Asunto(s)
Apoptosis , Fosfatidilinositol 3-Quinasas , Proliferación Celular , Glucólisis , Humanos , Fosfatidilinositol 3-Quinasas/metabolismo , Piruvato Quinasa
18.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(5): 1485-1492, 2021 Oct.
Artículo en Chino | MEDLINE | ID: mdl-34627428

RESUMEN

OBJECTIVE: To explore the regulatory effect of TRIP13 on the proliferation and apoptosis of B-cell lymphoma cells and its possible molecular mechanism by knocking down/overexpressing TRIP13 on the cell lines Granta-519 and JVM-2. METHODS: Lentiviral transfection technology was used to construct Granta-519 and JVM-2 cells with knocked down or overexpressed TRIP13 and their control cells. The efficiency of transfection was determined by fluorescence microscopy. The efficiency of knockdown and overexpression was evaluated by real-time quantitative PCR and Western blot. The proliferation was detected by CCK-8 assay. The apoptosis was detected by the Annexin V-APC single staining. The cell cycle was detected by the PI staining. The expression levels of P53, MDM4, and BCL-2 were evaluated by Western blot. RESULTS: After TRIP13 was knocked down, the proliferation ability of Granta-519 and JVM-2 cells was significantly reduced, and the apoptosis rate significantly increased. After TRIP13 was overexpressed, the proliferation ability of Granta-519 and JVM-2 cells was significantly enhanced, and the apoptosis was significantly reduced. After TRIP13 was knocked down, Granta-519 cells had obvious G1 phase arrest, and JVM-2 cells had obvious G1 and G2/M phase arrest. After TRIP13 was knocked down in Granta-519 cells, the expression of BCL-2 protein decreased, while MDM4 protein increased. After TRIP13 was overexpressed, the expression of MDM4 protein decreased. After TRIP13 was overexpressed in JVM-2 cells, the expression of BCL-2 protein increased. CONCLUSION: TRIP13 promotes the proliferation of B-cell lymphoma cells, inhibits their apoptosis, and affects their proliferation and apoptosis by participating in the regulation of the cell cycle. TRIP13 promotes the expression of BCL-2 proteins and inhibits the expression of MDM4 protein in B-cell lymphoma cells.


Asunto(s)
Proteínas de Ciclo Celular , Linfoma de Células B , ATPasas Asociadas con Actividades Celulares Diversas/metabolismo , Apoptosis , Proliferación Celular , Humanos , Proteínas Proto-Oncogénicas
19.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(5): 1504-1509, 2021 Oct.
Artículo en Chino | MEDLINE | ID: mdl-34627431

RESUMEN

OBJECTIVE: To investigate the effect of arsenic disulfide (AS2S2) combined with itraconazole on the proliferation, apoptosis and hedgehog pathway of diffuse large B-cell lymphoma (DLBCL) cells. METHODS: The human DLBCL cell OCI-LY3 was treated with different concentrations of AS2S2 and itraconazole. Cell proliferation inhibition was detected by CCK-8, cell apoptosis rate was determined by flow cytometry. The expression levels of BCL-2, BAX, SMO and GLi1 were detected by Western blot. RESULTS: The DLBCL cell viability was decreased significantly at 24, 48 or 72 h as cultured with itraconazole. Along with the increasing of itraconazole concentration, the DLBCL cell viability was significantly reduced as compared with that in control group, and the results showed statistically significant(r=-0.690,r=-0.639, r=-0.833, r=-0.808, r=-0.578). The inhibitory and apoptosis rates of the cells were significantly increased as compared with those of the single drug-treated group after treated by the combination of itraconazole and AS2S2(P<0.05). The protein levels of SMO and Glil were significantly down-regulated after treated by arsenic disulfide and itraconazole alone(P<0.01). The protein expression levels of SMO and Glil was down-regulated in the combined-treatment group(P<0.01). CONCLUSION: Itraconazole can inhibit proliferation of DLBCL cells in a concentration-and time-dependent manner. In addition, the combination of AS2S2 and itraconazole show a synergistic effects, which may be related with the down-regulated protein expression of SMO and Glil of Hedgehog signaling pathway.


Asunto(s)
Proteínas Hedgehog , Linfoma de Células B Grandes Difuso , Apoptosis , Arsenicales , Humanos , Itraconazol/farmacología , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Sulfuros
20.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(5): 1522-1527, 2021 Oct.
Artículo en Chino | MEDLINE | ID: mdl-34627434

RESUMEN

OBJECTIVE: To investigate the expression of cell division cycle protein 37 (Cdc37) in multiple myeloma (MM) and its effect on MM cell proliferation. METHODS: The expression of Cdc37 mRNA in CD138+ cells derived from 63 newly diagnosed MM patients and 8 healthy people were detected by real-time quantitative PCR (RT-qPCR). Cdc37 was down-regulated by lentivirus in MM cell line NCI-H929. CCK-8 assay and soft agar clone formation assay were conducted to explore the role of Cdc37 on MM proliferation in vitro. To further verify the effect of Cdc37 on MM cell proliferation in vivo, NOD/SCID mice subcutaneous tumorigenesis model was established. Flow cytometry was carried out to explore the role of Cdc37 on cell cycle. Cell cycle associated proteins and NF-κB pathway were detected by Western blot (WB). RESULTS: Cdc37 was highly expressed in newly diagnosed CD138+cells compared with healthy people. After Cdc37 suppression by shRNA lentivirus infection in NCI-H929 cells, the proliferation of MM cells were decreased in vitro and in vivo. Compared with the control group, the ratio of cells arrested in G0/G1 phase significantly increased in NCI-H929-Cdc37 shRNA cells, the expression of cyclin D1 decreased, while the expression of p21 and p53 was significantly up-regulated. Meanwhile, the activation of NF-κB signaling pathway was hampered in NCI-H929-Cdc37 shRNA cells. CONCLUSION: Cdc37 is highly expressed in newly diagnosed MM patients. Inhibition of Cdc37 results in decreased proliferation activity and G0/G1 arrest in NCI-H929 cells. The possible mechanism may be to inhibit the activation of NF-κB signaling pathway.


Asunto(s)
Mieloma Múltiple , Animales , Apoptosis , Proteínas de Ciclo Celular , Proliferación Celular , Chaperoninas , Humanos , Ratones , Ratones Endogámicos NOD , Ratones SCID
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