• Title/Summary/Keyword: cell cycle control

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Effects of Ubiquitin-conjugating Enzyme 2C on Invasion, Proliferation and Cell Cycling of Lung Cancer Cells

  • Tang, Xiao-Kui;Wang, Ke-Jian;Tang, Yu-Kui;Chen, Li
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.7
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    • pp.3005-3009
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    • 2014
  • The aims of this study were to investigate the influence of ubiquitin- conjugating enzyme E2C (UBE2C) on biological behavior of lung cancer cells. Using MTT, flow cytometry and invasion assays, we detected UBE2C expression and evaluated its biological properties in these cells, including effects on proliferation, the cell cycle profile and invasive capability. Compared with control cells, the UBE2C transfected cells demonstrated increased cellular proliferation (p<0.05). UBE2C transfected cells also had a lower percentage in G1 phase and a higher percentage in S phase (p<0.05). Importantly, the UBE2C transfected cells had a notable enhancement of cell numbers penetrating the basement membrane compared with the control group (p<0.05). Ectopic up-regulation UBE2C promoted the growth of lung cancer cells in vivo. Furthermore, we found UBE2C increased the expression of cyclin D1 and MMP-2. These results show UBE2C may represent a potential therapeutic target for lung cancer.

Review on Molecular and Chemopreventive Potential of Nimbolide in Cancer

  • Elumalai, Perumal;Arunakaran, Jagadeesan
    • Genomics & Informatics
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    • v.12 no.4
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    • pp.156-164
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    • 2014
  • Cancer is the most dreaded disease in human and also major health problem worldwide. Despite its high occurrence, the exact molecular mechanisms of the development and progression are not fully understood. The existing cancer therapy based on allopathic medicine is expensive, exhibits side effects; and may also alter the normal functioning of genes. Thus, a non-toxic and effective mode of treatment is needed to control cancer development and progression. Some medicinal plants offer a safe, effective and affordable remedy to control the cancer progression. Nimbolide, a limnoid derived from the neem (Azadirachta indica) leaves and flowers of neem, is widely used in traditional medical practices for treating various human diseases. Nimbolide exhibits several pharmacological effects among which its anticancer activity is the most promising. The previous studies carried out over the decades have shown that nimbolide inhibits cell proliferation and metastasis of cancer cells. This review highlights the current knowledge on the molecular targets that contribute to the observed anticancer activity of nimbolide related to induction of apoptosis and cell cycle arrest; and inhibition of signaling pathways related to cancer progression.

Induction of Cdk inhibitor p21 and inhibition of cyclooxygenase-2 by resveratrol in human lung carcinoma A549 cells. (Resveratrol에 의한 A549 인체 폐암세포의 증식억제 및 apoptosis 유발에 관한 연구)

  • 김영애;임선영;이숙희;박건영;이원호;최영현
    • Journal of Life Science
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    • v.14 no.5
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    • pp.800-808
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    • 2004
  • Resveratrol, a phytoalexin found at high levels in grapes and in grape products such as red wine, has been reported to possess a wide range of biological and pharmacological activities including antioxident, anti-inflammatory, anti-mutagenic, and anti-carcinogenic effects. According to recent studies, this compound is an effective inhibitor of cell growth in general, triggers partial arrest of the cell cycle and induce apoptosis. In this study, the anti-proliferative effects of resveratrol in A549 human lung carcinoma cells were investigated. It is shown that resveratrol induced the growth inhibition in a time-dependent manner and morphological changes of A549 cells, which were associated with induction of S phase arrest of the cell cycle and apoptotic cell death. The Bcl-$X_L$levels were markedly down-regulated in resveratrol treated cells, however, Bax and Bcl-2 were remained unchanged. Resveratrol treatment induced the proteolytic degradation of Sp-l and proliferating cell nuclear antigen protein, and inhibited the expression of $\beta$-catenin protein. Resveratrol treatment also induced a marked up-regulation of cyclin-dependent kinase (Cdk) inhibitor p21 and inhibited the kinase activities of Cdk2 and Cdk4. In addition, resveratrol treatment inhibited the levels of cyclooxygenase (COX)-2 mRNA and protein, and the release of prostagladin E2 without alteration of COX-1 expression. Taken together, these findings suggest that resveratrol may be a potential chemotherapeutic agent for the control of human lung carcinorma cells.

Effects of Duchesnea Indica of Colorectal Adenocarcinoma Cells (사매가 대장암 세포에 미치는 영향)

  • Lee, Do-Hyoung;Kim, Jin-Sung;Yoon, Sang-Hyub;Ryu, Ki-Won;Ryu, Bong-Ha
    • The Journal of Internal Korean Medicine
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    • v.26 no.2
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    • pp.310-319
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    • 2005
  • Objectives: The aim is to identify any anti-tumor effects of Duchesnea indica(Andr.) Focke on colon cancer cells. Materials & Methods: Colo201 human adenocarcinoma cells were obtained from American Type Culture Collection. The boiled extract of Duchesnea indica(Andr.) Focke was added (10 and 20 microliters) to cultures and observed at 0, 6, and 12 hours, and at 12-hour intervals thereafter. Morphological changes in colon cancer cells were observed through an inverted microscope, Destruction of colon cancer cells was measured through Trypan blue exclusion testing. Suppression of the viability of colon cancer cells were measured via MTT assay. Anti-cancer mechanisms in the cell cycle of colon cancer cells were analysed via flow cytometry. Results: After introduction of Duchesnea indica(Andr.) Focke to cultures several changes were seen. Significant atrophy of the nucleus and cytoplasm of colon cancer cells was observed, indicating cell injury. Destruction of colon cancer cells was observed in direct proportion to dosage and duration. Suppression of viability of colon cancer cells for each test group was greater than that of the control group increasingly over time(36h, 48h, 60h, 72h), which was statistical significant (p<0.05). Cell numbers of the mitosis phase of the colon cancer cell cycle reduced. Conclusions: Statistcally significant anti-tumor effects of Duchesnea indica(Andr.) Focke were observed in this in vitro experiment. Results support a role for Duchesnea indica(Andr.) Focke in treatment of colon cancer. though it will required progressive research to develop a practical treatment.

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Gene Microarray Assessment of Multiple Genes and Signal Pathways Involved in Androgen-dependent Prostate Cancer Becoming Androgen Independent

  • Liu, Jun-Bao;Dai, Chun-Mei;Su, Xiao-Yun;Cao, Lu;Qin, Rui;Kong, Qing-Bo
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.22
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    • pp.9791-9795
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    • 2014
  • To study the gene expression change and possible signal pathway during androgen-dependent prostate cancer (ADPC) becoming androgen-independent prostate cancer (AIPC), an LNCaP cell model of AIPC was established using flutamide in combination with androgen-free environment inducement, and differential expression genes were screened by microarray. Then the biological process, molecular function and KEGG pathway of differential expression genes are analyzed by Molecule Annotation System (MAS). By comparison of 12,207 expression genes, 347 expression genes were acquired, of which 156 were up-ragulated and 191 down-regulated. After analyzing the biological process and molecule function of differential expression genes, these genes are found to play crucial roles in cell proliferation, differntiation, cell cycle control, protein metabolism and modification and other biological process, serve as signal molecules, enzymes, peptide hormones, cytokines, cytoskeletal proteins and adhesion molecules. The analysis of KEGG show that the relevant genes of AIPC transformation participate in glutathione metabolism, cell cycle, P53 signal pathway, cytochrome P450 metabolism, Hedgehog signal pathway, MAPK signal pathway, adipocytokines signal pathway, PPAR signal pathway, TGF-${\beta}$ signal pathway and JAK-STAT signal pathway. In conclusion, during the process of ADPC becoming AIPC, it is not only one specific gene or pathway, but multiple genes and pathways that change. The findings above lay the foundation for study of AIPC mechanism and development of AIPC targeting drugs.

Protection of rainbow trout (Oncorhynchus mykiss) against infectious hematopoietic necrosis virus (IHNV) by immunization with G gene's cytoplasmic and transmembrane region-deleted single-cycle IHNV

  • Jae Young, Kim;Jun Soung, Kwak;Hyoung Jun, Kim;Ki Hong, Kim
    • Journal of fish pathology
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    • v.35 no.2
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    • pp.157-165
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    • 2022
  • Single-cycle viruses generated by reverse genetic technology are replication-incompetent viruses due to the elimination of gene(s) essential for viral replication, which provides a way to overcome the safety problem in attenuated viruses. Infectious hematopoietic necrosis virus (IHNV) is a major pathogen causing severe damage in cultured salmonid species. In the present study, we generated a single-cycle IHNV lacking the transmembrane and cytoplasmic domain in the G gene (rIHNV-GΔTM) and evaluated the prophylactic potential of rIHNV-GΔTM in rainbow trout (Oncorhynchus mykiss). To produce rIHNV-GΔTM, IHNV G protein-expressing Epithelioma papulosum cyprini (EPC) cells were established. However, as the efficiency of rIHNV-GΔTM production in EPC cell clones was not high, fish were immunized with a low-tittered single-cycle virus (1.5 × 102 PFU/fish). Despite the low dose, the single-cycle IHNV induced significant protection in rainbow trout against IHNV infection, suggesting high immunogenicity of rIHNV-GΔTM. No significant difference in serum ELISA titers against IHNV between the rIHNV-GΔTM immunized group and the control group suggests that the immunized dose of rIHNV-GΔTM might be too low to induce significant humoral adaptive immune responses in rainbow trout. The involvement of adaptive cellular immunity or innate immunity in the present significantly higher protection by the immunization with rIHNV-GΔTM should be further investigated to know the protection mechanism.

Mangiferin Induces Apoptosis by Regulating Bcl-2 and Bax Expression in the CNE2 Nasopharyngeal Carcinoma Cell Line

  • Pan, Li-Li;Wang, Ai-Yan;Huang, Yong-Qi;Luo, Yu;Ling, Min
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.17
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    • pp.7065-7068
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    • 2014
  • To investigate the anti-proliferative mechanism of mangiferin in a human nasopharyngeal carcinoma cell line, CNE2 cells were incubated with different concentrations of mangiferin (12.5, 25, 50, 100, 150 and $200{\mu}M$) or with PBS as a control for 72 hours. Analyses were made of the cell cycle and apoptosis with measurement of mRNA and protein levels of two apoptosis-related genes, Bcl-2 and Bax. Flow cytometry assays showed mangiferin could inhibit CNE2 cell proliferation via G2/M arrest and induction of early apoptosis. Real time PCR and Western blotting showed the mRNA and protein level of Bcl-2 to be down-regulated, while those of Bax were upregulated, when CNE2 cells were treated with mangiferin. This investigation indicated anti-proliferation effects of mangiferin through induction of cell apoptosis regulated by Bcl-2 and Bax expression.

On Thermal and State-of-Charge Balancing using Cascaded Multi-level Converters

  • Altaf, Faisal;Johannesson, Lars;Egardt, Bo
    • Journal of Power Electronics
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    • v.13 no.4
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    • pp.569-583
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    • 2013
  • In this study, the simultaneous use of a multi-level converter (MLC) as a DC-motor drive and as an active battery cell balancer is investigated. MLCs allow each battery cell in a battery pack to be independently switched on and off, thereby enabling the potential non-uniform use of battery cells. By exploiting this property and the brake regeneration phases in the drive cycle, MLCs can balance both the state of charge (SoC) and temperature differences between cells, which are two known causes of battery wear, even without reciprocating the coolant flow inside the pack. The optimal control policy (OP) that considers both battery pack temperature and SoC dynamics is studied in detail based on the assumption that information on the state of each cell, the schedule of reciprocating air flow and the future driving profile are perfectly known. Results show that OP provides significant reductions in temperature and in SoC deviations compared with the uniform use of all cells even with uni-directional coolant flow. Thus, reciprocating coolant flow is a redundant function for a MLC-based cell balancer. A specific contribution of this paper is the derivation of a state-space electro-thermal model of a battery submodule for both uni-directional and reciprocating coolant flows under the switching action of MLC, resulting in OP being derived by the solution of a convex optimization problem.

Efficacy and Safety of Pemetrexed in Advanced Non-Small Cell Lung Carcinoma (진행성 비소세포폐암 환자에서 Pemetrexed의 효과와 안전성)

  • Lee, Gyu Jin;Jung, Mann Hong;Jang, Tae Won;Ok, Chul Ho;Jung, Hyun Joo
    • Tuberculosis and Respiratory Diseases
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    • v.67 no.2
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    • pp.121-126
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    • 2009
  • Background: Pemetrexed has been prescribed newly as a second line chemotherapy in advanced non-small cell lung carcinoma (NSCLC). The aim of study was to determine the efficacy and toxicity of pemetrexed in advanced NSCLC. Methods: Patients with histologically or cytologically confirmed NSCLC were evaluated from June 2006 to December 2008. The patients had relapsed or progressed after prior chemotherapy treatment. They were treated with intravenous pemetrexed $500mg/m^2$ for 10 min on Day 1 of each 21-day cycle. Results: A total of 89 patients were eligible for analysis. The response rate and disease control rate were 11% and 66%. Non-squamous cell carcinoma histology was significantly associated with a superior response rate (p=0.035) and disease control rate (p=0.009) than squamous cell carcinoma histology. The median survival time was 13 months and the median progression free survival time was 2.3 months. The median survival time of patients with ECOG PS 0~1 was 13.2 months, whereas median survival time was 11.6 months for patients with PS 2 (p=0.002). The median progression free survival time of patients with PS 0~1 were 3.8 months, but 2.1 months for patients with PS 2 (p=0.016). The median progression free survival time of smokers with non-squamous cell carcinoma was 3.4 months, which was significant (p=0.014). Grade 3~4 neutropenia were seen in 7.9% patients. Conclusion: Pemetrexed has efficacy in patients who had prior chemotherapy with advanced NSCLC and less hematologic toxicity.

The Effects of Bee Venom & Melittin on Cell Death in Neuroblastoma Cell Line (Bee Venom 및 Melittin 약침액(藥鍼液)이 신경아세포종(神經芽細胞腫)의 세포사(細胞死)에 미치는 영향(影響))

  • Kang, Dong-cheol;Jung, Tae-young;Seo, Jung-chul;Leem, Seong-cheol;Han, Sang-won
    • Journal of Acupuncture Research
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    • v.20 no.2
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    • pp.98-111
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    • 2003
  • Objective : This study was designed to analyze the effects of bee venom and melittin on cell death in neuroblastoma cell line. Methods : MTT assay, morphologic method, DNA fragmentation, flow cytometry, immunocytochemistry analysis, RT-PCR and Western blot were performed. Results : The obtained results are summarized as follows: 1. The MTT assay demonstrated that neuroblastoma cell viability was significantly inhibitted dose-dependently by treatment with bee venom and melittin in comparison with control. 2. Cell culture demonstrated that control group proliferated highestly at he 5th day in comparison with the 4th day in bee venom and melittin group. And in bee venom and melitti group cell proliferation decreased 2.5 times than control group. 3. The morphologic study demonstrated that neuroblastoma cell showed apoptosis after treatment with bee venom and melittin for 6 hours using microscope. 4. The Flow cytometry demonstrated that apoptosis of neuroblastoma cell treated with bee venom and melittin was related with stop of cell cycle in stage of $G_0/G_1$. 5 .DNA fragmenation demonstrated that neuroblastoma cell treated with bee venom and melittin showed DNA ladder below 1 Kbp. 6. Immunocytochemistry assay demonstrated that Fos and MAPK which are related with cancer were down-regulated by treatment with bee venom and melittin. 7. RT-PCR analysis demonstrated that Fos and MAPK mRNA were transcripted. Fos was down-regulated form treatment with $5{\mu}g/ml$ bee venom and MAPK was down-regulated form $1{\mu}g/ml$ bee venom. 8. Western blot demonstrated that Fos was down-regulated from $1{\mu}g/ml$ bee venom whereas MAPK was expressed by $1{\mu}g/ml$ bee venom but down-regulated by $10{\mu}g/ml$ bee venom. Conclusions : We found that some cancer related genes ware down-regulated by treatment with bee venom and melittin. Further study is needed for investigating the anti-cancer effect of bee venom and melittin.

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