Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P42574 (caspase-3)
 45,978 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Esophageal cancer is one of the most aggressive malignancies with poor prognosis. The administration of the first- and second-generation platinum drugs is frequently accompanied by drug resistance and severe toxicity. The aim of present study is to investigate the anti-tumor activity of the third-generation platinum drug Lobaplatin against esophageal squamous cell carcinoma in vitro and in vivo, and clarify the underlying molecular mechanism. The cytotoxicity of Lobaplatin against esophageal squamous cell carcinoma cell lines was determined by the MTT and clonogenic assay. Cell apoptosis was assessed by Annexin V-FITC/PI apoptosis assay using flow cytometry. The expression of proteins was determined by western blot analysis. The in vivo anti-tumor activity was evaluated in nude mice xenograft. Lobaplatin significantly inhibited the growth of KYSE-410 and EC-109 cells in a dose- and time-dependent manner and induced cell apoptosis by increasing expressions of cleaved-caspase-3, cleaved-caspase-8, cleaved-caspase-9 and Bax, decreasing expression of Bcl-2. In vivo study showed that Lobaplatin suppressed tumor growth of EC-109 xenograft. Lobaplatin significantly inhibited the growth of esophageal squamous cell carcinoma by inducing apoptosis through the caspase-dependent pathway. Lobaplatin is an effective anti-cancer agent against esophageal cancer.
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PMID:Antitumor activity of Lobaplatin against esophageal squamous cell carcinoma through caspase-dependent apoptosis and increasing the Bax/Bcl-2 ratio. 2886 64

Comprehensive gene screening with transposons is a novel procedure for the systematic identification of resistant genes. The present study aimed to use this technique to identify candidate radioresistant genes in esophageal squamous cell carcinoma. A transposon is a base sequence that can translocate to another location in the genome at random. By inserting the cytomegalovirus promotor as a transcriptional activator in the transposon, the following gene in the new location becomes overexpressed and the gene located at the transposon insertion site is downregulated. Consequently, various transposon-tagged cells, which have differentially overexpressed or downregulated genes using the transposon method can be obtained. Following the irradiation of transposon-tagged cells, candidate radioresistant genes can be selected in order to detect the location of the transposon in the cells that have survived. A total of 11 genes were detected as candidate radioresistant genes. Cytochrome c oxidase 1 (MT-CO1), an enzyme involved in apoptosis through the activation of the caspase cascade, was one of the candidate genes identified. The relative expression level of MT-CO1 was 0.12 in MT-CO1-downregulated cells which was significantly lower compared with the expression level in parent TE4 cells (P<0.001). The survival rate was 28.7% in MT-CO1-downregulated cells and 10.5% in parent TE4 cells 9 days following 5-Gy irradiation. The activity of cytochrome c and caspase-3 following irradiation was significantly lower in the MT-CO1-downregulated radioresistant cells compared with in TE4 cells. In conclusion, the novel gene screening technique demonstrated to be useful for detecting candidate radioresistant genes in esophageal squamous cell carcinoma. The results of the present study revealed that the downregulation of MT-CO1 induced radioresistance occurs by inhibiting the activation of the caspase cascade in radioresistant esophageal cancer cells.
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PMID:Downregulation of cytochrome c oxidase 1 induced radioresistance in esophageal squamous cell carcinoma. 2894 30

Epigallocatechin-3-gallate (EGCG) is a component of green tea with anticancer effects that have been demonstrated in multiple types of cancer, but few reports exist concerning its effect in esophageal squamous cell carcinoma cells. The present study investigated apoptosis induced by EGCG treatment and the underlying molecular mechanisms in Eca109 and Ec9706 human esophageal squamous cell carcinoma cells. The apoptosis rate following treatment with various concentration of EGCG for 24 h was detected by flow cytometry. The effect of EGCG on esophageal cancer cell viability was detected via MTT assay. Mitochondrial membrane potential and caspase-3 protein expression was detected in Eca109 and Ec9706 cells following treatment with EGCG by flow cytometry. The telomerase activity of Eca109 and Ec9706 cells following treatment with EGCG was assayed using the polymerase chain reaction-telomeric repeat amplification protocol (PCR-TRAP) argentation method. EGCG was demonstrated to inhibit the viability of Eca109 and Ec9706 cells in a dose-and time-dependent manner. The flow cytometry results revealed that EGCG treatment induced apoptosis, decreased the mitochondrial membrane potential and increased caspase-3 protein expression levels. PCR-TRAP argentation analysis revealed that EGCG inhibited telomerase activity. The results of the present study suggested that EGCG functions as an antitumor agent in esophageal cancer cells. The induction of apoptosis may be a viable method for treating esophageal cancer. It is possible to induce apoptosis by modulating the expression level of telomerase activity, mitochondrial membrane potential and caspase-3 protein expression levels.
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PMID:Epigallocatechin-3-gallate suppresses cell proliferation and promotes apoptosis in Ec9706 and Eca109 esophageal carcinoma cells. 2894 54

Evidence for demonstrating the role of the green tea component epigallocatechin-3-gallate (EGCG) in esophageal squamous cell carcinoma cells is limited. In this study, we investigated apoptosis induced by EGCG and the underlying molecular mechanisms in human esophageal squamous cell carcinoma cells. The growth-inhibitory effects of EGCG on esophageal cancer cell (Eca109 and Ec9706) were detected by MTT. Using flow cytometry, we determined the cellular apoptosis, bcl-2, bax and caspase-3 protein expression in Eca109 and Ec9706 cells following treatment with EGCG for 24h. After treatment of Eca109/ABCG2 (an esophageal cancer multidrug resistance cell line) cells with adriamycin (ADM) combined with EGCG for 24h, the cellular apoptosis, mitochondrial membrane potential, ADM concentration in cells and ABCG2 protein expression were detected by flow cytometry. EGCG inhibited the growth of Eca109 and Ec9706 cells in a dose- and time- dependent manner. EGCG induced apoptosis, decreased the bcl-2 protein expression and increased the expression of bax and caspase-3 protein. The rate of apoptosis and ADM concentration in the Eca109/ABCG2 cells following treatment with ADM and EGCG were higher than that with ADM treatment alone, although the mitochondrial membrane potential was significantly lower (P<0.01). EGCG reduced the ABCG2 expression of Eca109/ABCG2 cells. Our data indicated that EGCG inhibited cell growth and induced esophageal cancer cell apoptosis. It reduced the bcl-2 protein expression and increased the bax and caspase-3 protein expression. EGCG reversed multi-drug resistance by reducing ABCG2 expression and increasing the anticancer drug concentration in cancer cells.
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PMID:Epigallocatechin-3-gallate promotes apoptosis and reversal of multidrug resistance in esophageal cancer cells. 2896 74

Esophageal cancer is a common tumor for which morbidity and mortality are high worldwide. We aimed to study alterations in miR-486 expression in esophageal cancers, and the effect miR-486 on esophageal cancer cell function and behavior. We collected esophageal cancer tissues/corresponding normal tissues from 20 patients and utilized three esophageal cancer cell lines and normal esophageal epithelial cells, and the expression of miR-486, CDK4 and BCAS2 was detected by qRT-PCR. Western blotting was used to detect the expression of CDK4 and BCAS2 protein. Then, we overexpressed miR-486 in esophageal cancer cell line EC9706. A series of cell functional analyses, including cell growth, cell cycle, apoptosis, migration and invasion were performed in esophageal cancer cells using colony formation assay, flow cytometry, Transwell and scratch assays, respectively. Dual-luciferase reporter gene assay was used to detect the target genes of miR-486. We found that the expression of miR-486 in esophageal cancer tissues and cell lines was significantly lower than that in the normal tissues and normal esophageal epithelial cell line. Overexpression of miR-486 significantly inhibited the colony formation ability, induced G0/G1 phase arrest and apoptosis and suppressed cell migration and invasion in the EC9706 cells. Using bioinformatics and luciferase reporter assay, we identified that CDK4 and BCAS2 may be target genes of miR-486 and levels of CDK4 and BCAS2 were both significantly higher in the esophageal cancer tissues and cell lines than levels in the normal tissues and cells. Furthermore, knockdown of CDK4/BCAS2 coincided with the suppressive effects of miR-486 in esophageal cancer cells. Expression of apoptotic signaling molecules p21 and caspase-3 was upregulated in the CDK4/BCAS2-knockdown groups. These results suggest that miR-486 may suppress tumor cell growth and metastasis in esophageal cancer by targeting CDK4/BCAS2. The newly identified miR-486/CDK4/BCAS2 pathway provides further insight into the development and progression of esophageal cancer, which is of great significance to the early diagnosis and detection of esophageal cancer.
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PMID:miR-486 functions as a tumor suppressor in esophageal cancer by targeting CDK4/BCAS2. 2911 64

Acquired radioresistance compromises the efficacy of radiotherapy for carcinomas including esophageal cancer (EC), thus resulting in recurrence and poor survival. Recent research corroborated radiosensitive function of simvastatin in stem-like breast cancer cells. However, its role in EC radioresistance remains poorly elucidated. Here, we developed a radioresistant EC cell line Ec9706-R with higher resistance to irradiation relative to control Ec9706 cells. Intriguingly, Ec9706-R cells exhibited epithelial-mesenchymal transition (EMT) characteristics with high invasion and migration ability. Simvastatin sensitized radioresistance of Ec9706-R cells and suppressed cell proliferation, but aggravated radiation-induced apoptosis and caspase-3 activity. Furthermore, simvastatin reversed EMT and inhibited cell invasion and migration of Ec9706-R cells. Mechanism assay confirmed the activation of PI3K/AKT pathway after radiation, which was inhibited by simvastatin. After restoring this pathway by its activator, IGF-1, simvastatin-mediated radiosensitivity and EMT reversion were abrogated. Further assay substantiated the PTEN suppression after irradiation, which was elevated following simvastatin pre-treatment. Moreover, PTEN cessation attenuated the inhibitory effect of simvastatin on PI3K/AKT activation, and subsequently antagonized simvastatin-induced radiosensitivity and EMT reversion. Additionally, simvastatin aggravated radiation-mediated Ec9706-R tumor growth inhibition. Together, simvastatin inhibits the development of Ec9706-R cells by increasing radiosensitivity and reversing EMT via PTEN-PI3K/AKT pathway, implying a promising strategy against EC radioresistance.
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PMID:Simvastatin inhibits the development of radioresistant esophageal cancer cells by increasing the radiosensitivity and reversing EMT process via the PTEN-PI3K/AKT pathway. 2920 61

In this study, we examined the molecular and functional characterization of choline uptake in the human esophageal cancer cells. In addition, we examined the influence of various drugs on the transport of [3H]choline, and explored the possible correlation between the inhibition of choline uptake and apoptotic cell death. We found that both choline transporter-like protein 1 (CTL1) and CTL2 mRNAs and proteins were highly expressed in esophageal cancer cell lines (KYSE series). CTL1 and CTL2 were located in the plasma membrane and mitochondria, respectively. Choline uptake was saturable and mediated by a single transport system, which is both Na+-independent and pH-dependent. Choline uptake and cell viability were inhibited by various cationic drugs. Furthermore, a correlation analysis of the potencies of 47 drugs for the inhibition of choline uptake and cell viability showed a strong correlation. Choline uptake inhibitors and choline deficiency each inhibited cell viability and increased caspase-3/7 activity. We conclude that extracellular choline is mainly transported via a CTL1. The functional inhibition of CTL1 by cationic drugs could promote apoptotic cell death. Furthermore, CTL2 may be involved in choline uptake in mitochondria, which is the rate-limiting step in S-adenosylmethionine (SAM) synthesis and DNA methylation. Identification of this CTL1- and CTL2-mediated choline transport system provides a potential new target for esophageal cancer therapy.
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PMID:Molecular and Functional Characterization of Choline Transporter-Like Proteins in Esophageal Cancer Cells and Potential Therapeutic Targets. 2922 41

A previous study has reported that frequent amplifications of the TG-interacting factor (TGIF) were observed in esophageal squamous cell carcinoma. The aim of the present study was to investigate the potential role of TGIF in the proliferation and tumorigenicity of the esophageal cancer cell line EC109 and cisplatin-induced apoptosis. Stable TGIF-knockdown EC109 cell line was established by infecting short hairpin RNA (shRNA) lentiviral particles. Soft agar and tumor xenograft assays were applied in nude mice. Flow cytometry was employed to evaluate the cell cycle and apoptosis. Western blot analysis was used to detect the expression of proteins. TGIF knockdown suppressed EC109 cell proliferation, colony formation in soft agar and tumor growth in nude mice, induced cell cycle arrest in the G1 phase, and promoted cisplatin-induced apoptosis. In addition, TGIF knockdown significantly reduced the expression of phospho-Rb in EC109 cells. The reduced level of full length PARP expression and the increased level of cleaved caspase-3 expression were observed in EC109 cells with the treatment of cisplatin and TGIF knockdown. The results suggest that knockdown of TGIF attenuated the proliferation and tumorigenicity of EC109 cells, and promoted cisplatin-induced apoptosis.
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PMID:Knockdown of TGIF attenuates the proliferation and tumorigenicity of EC109 cells and promotes cisplatin-induced apoptosis. 2934 16

Matrine, as a natural alkaloid isolated from the traditional herb medicine sophora flavescens, has been proved to possess excellent biological activities, including anticancer effects. Now, this research aims to assess the anticancer activities and the mechanism of matrine against esophageal cancer cells, we investigated the proliferative inhibition, apoptosis induction, as well as the underlying mechanism of matrine on esophageal cancer KYSE-150 cells. It was found that matrine could suppress KYSE-150 cell proliferation and significantly mediate cell apoptosis in a dose-dependent relation by increasing intracellular reactive oxygen species level and triggering mitochondrial membrane potential disruption. More precise mechanism studies demonstrated that matrine could up-regulate the expression of Bax proteins and down-regulate the expression of Bcl-2 proteins, as well as the activation about caspase-3, 8 and 9 in KYSE-150 cells. The morphological analysis of KYSE-150 cells exhibited that matrine could destroy the F-actin and nuclei structures and induce morphological damage with increased surface height distribution and roughness of cell membrane. These results not only demonstrated the potential anticancer activity mechanism of matrine at nanoscale, but also provide preliminary guidance for the treatment of esophageal cancer using matrine.
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PMID:Chinese herb medicine matrine induce apoptosis in human esophageal squamous cancer KYSE-150 cells through increasing reactive oxygen species and inhibiting mitochondrial function. 2956 33

Paclitaxel (PTX) has been used in a variety of malignancies for inhibiting tumor development and improving survival. However, its clinical application is limited due to poor solubility, drug resistance, and gastrointestinal reactions. Natural borneol (NB), as a promoter, could help to improve drug absorption. Therefore, the aims of the present study were to investigate the ability of NB to synergize with PTX to induce human esophageal squamous cell carcinoma (ESCC) cells apoptosis and the underlying mechanism of synergistic effects. In this study, our findings showed that NB could effectively synergize with PTX to inhibit the survival of ESCC cells by inducing apoptosis. The molecular mechanism by western blotting elucidated that combination treatment with PTX and NB significantly activated apoptotic pathway by triggering upregulation of cleaved caspase-3 expression and downregulation of survivin and P-AKT expression. These results demonstrated that NB could strongly potentiate PTX-induced apoptosis in ESCC cells through suppressing PI3K/AKT pathway. Thus, the combination therapy with NB and PTX might be a promising treatment strategy for human esophageal cancer.
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PMID:Natural Borneol Enhances Paclitaxel-Induced Apoptosis of ESCC Cells by Inactivation of the PI3K/AKT. 2966 Aug 11


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