• Title/Summary/Keyword: Bcl-2

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BCL2L10 Protein Induces Apoptosis in KGN-Human Granulosa Cells (KGN(난소과립세포)에서 BCL2L10 단백질의 세포사멸 유도 기능 연구)

  • Kim, Jae-Hong;Lee, Kyung-Ah;Bae, Jee-Hyeon
    • Development and Reproduction
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    • v.15 no.2
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    • pp.113-120
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    • 2011
  • BCL-2 family essential proteins to play a pivotal role to perform in apoptosis signaling pathways and essential proteins for the regulation of cell death. BCL2L10 protein is a member of BCL-2 family and it regulates both anti-apoptotic and pro-apoptotic function of specific tissue or cell line. BCL2L10 of function and expression is not reported in ovary cell lines. In this study we reported that BCL2L10 were significant expression of KGN cell line. Ectopic expression of BCL2L10 induced cell death, and its cells killing effect was blocked by pan-caspase inhibitor of the Z-VAD-fmk. Ectopic expression of BCL2L10 protein led to the activation of caspase 9 and caspase 3, suggesting apoptotic cell death, and confocal microscopic analyses showed that BCL2L10 was partially localized in mitochondria. Thus, we provide a novel function of BCL2L10 in KGN cells, which was involved in the intrinsic cell death pathway.

Expression of bcl-2 in Non-small Cell Lung Cancer and its Effects on Cell Proliferation and Survival (비소세포 폐암에서 bcl-2의 발현률과 세포분열주기 및 예후에 미치는 영향)

  • Kuk, Hiang;Koh, Hyeck-Jae;Gu, Ki-Seon;Jeong, Eun-Taik
    • Tuberculosis and Respiratory Diseases
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    • v.46 no.1
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    • pp.36-43
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    • 1999
  • Background : Tumor growth is the net result of intrinsic proliferation and escape from active cell death. bcl-2 is a member of a new category of oncogenes that is not involved in influencing cell proliferation but is involved in regulating cell death(apoptosis). Based on this information, it seems to be reasonable to expect that there may be clinical prognostic significance of bcl-2 expression in non-small cell lung cancer. But its prognostic significance is not established. Methods: To investigate the role of bcl-2 in lung cancer, we performed immunohistochemical stain of bcl-2 on 57 biopsy specimens from resected primary non-small cell lung cancer. Thereafter, flow cytometric cell cycle analysis was done. And we analyzed the correlation between bcl-2 expression, clinical parameters, S-, $G_1$-phase fraction and survival. Results: bcl-2 were detected in 43.8% of total 57 patients(according to histology, squamous cancer 47%, adenocarcinoma 32%, according to TNM stage, I 28.6%, II 52.3%, III 45.5%. both differences were insignificant). By using the flow cytometric analysis, mean S-phase fraction of bcl-2(+) and (-) group were 14.1($\pm7.8$)%, 24.7($\pm10.5$)% (p<0.005), mean $G_1$-phase fraction of bcl-2(+) and bcl-2(-) group were 75.5($\pm10.8$)%, 65.5($\pm11.4$)%(p<0.05). 2yr, 3yr and 5yr survival and median survival time of bcl-2(+) group were 65%, 54%, 41%, 53 months, and those of bcl-2(-) group were 71%, 52%, 46%, 37 months. (p>0.05, Kaplan-Meier, log rank) Conclusion: bcl-2 was detected in 43.8% of primary non-small cell lung cancer. The S-phase fraction of bcl-2(+) group was less than bcl-2(-) group, and G1-phase fraction of bcl-2(+) group was more than bcl-2(-) group. But, expression of bcl-2 could not be a prognostic factor.

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HS-1200 Overcomes the Resistance Conferred by Bcl-2 in Human Leukemic U937 Cells

  • Park, Jun-Young;Moon, Jeong-Bon;Kim, In-Ryoung;Kim, Gyoo-Cheon;Park, Bong-Soo;Kwak, Hyun-Ho
    • International Journal of Oral Biology
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    • v.37 no.3
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    • pp.91-102
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    • 2012
  • Bcl-2 protects tumor cells from the apoptotic effects of various anti-neoplastic agents. Increased expression of Bcl-2 has been associated with a poor response to chemotherapy in various malignancies, including leukemia. Hence, bypassing the resistance conferred by anti-apoptotic factors such as Bcl-2 represents an attractive therapeutic strategy against cancer cells, including leukemic cells. This study was undertaken to examine whether the anticancer drug, cisplatin and the synthetic chenodeoxycholic acid (CDCA) derivative, HS-1200 show anti-tumor activity in U937 and U937/Bcl-2 cells. Viability assays revealed that HS-1200 overcomes the resistance conferred by Bcl-2 in human leukemic U937 cells. Various apoptosis assessment assays further demonstrated that HS-1200 overcomes the resistance conferred by Bcl-2 in human leukemic U937 cells by inducing apoptosis. In addition HS-1200, but not cisplatin, overcomes the anti-apoptotic effects of Bcl-2 in Bcl-2 over-expressing human leukemic cells (U937/Bcl-2 cells). Notably, we observed that the HS-1200-induced formation of mature promyelocytic leukemia (PML) nuclear bodies (NBs) correlates with a suppression of the anti-apoptotic effects of Bcl-2 in human leukemic cells over-expressing this protein (U937/Bcl-2 cells). Furthermore, HS-1200 was found to induce the association between PML and SUMO-1, Daxx, Sp100, p53 or CBP in the aggregated PML-NBs of U937/Bcl-2 cells. Thus, PML protein and the formation of mature PML-NBs could be considered as therapeutic targets that may help to bypass the resistance to apoptosis conferred by Bcl-2. Elucidating the exact mechanism by which PML regulates Bcl-2 will require further work.

Effects of Bcl-2 Overexpressing on the Apoptotic Cell Death Induced by HDAC Inhibitors in Human Leukemic U937 Cells (HDAC 저해제에 의한 인체 백혈병 U937 세포의 apoptosis 유발에 미치는 Bcl-2의 영향)

  • Lee, In-Hyuk;Hur, Man-Gyu;Park, Dong-Il;Choi, Byung-Tae;Choi, Yung-Hyun
    • Journal of Life Science
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    • v.17 no.4 s.84
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    • pp.552-560
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    • 2007
  • Histone deacetylase (HDAC) is overexpressed in a variety of cancers and is closely correlated with oncogenic factors. HDAC inhibitors such as trichostatin A(TSA) and sodium butyrate (Na-B) have been shown to induce apoptosis in vitro and in vivo in many cancer cells. The anti-apoptotic Bcl-2 protein has the remarkable ability to prevent cell death and Bcl-2 overexpression has been reported to protect against cell death. We previously reported that the apoptotic cell death of human leukemic U937 cells by TSA and Na-B treatment was associated with the down-regulation of Bcl-2 expression and activation of caspases. In the present study, we investigated the effects of Bcl-2 overexpression on the growth inhibition, cell cycle arrest and apoptosis induced by TSA and Na-B in U937 cells. TSA-induced growth inhibition, cell cycle arrest and apoptosis were significantly attenuated in Bcl-2 overexpressing U937/Bcl-2 cells however Na-B did not affected. Induction of apoptosis by TSA was accompanied by down-regulation of Bcl-2 expression, activation of caspase-3, -8 and -9, and degradation of DNA fragmentation factor/inhibitor of caspase-activated DNase, which was blocked by the overexpression of Bcl-2. Collectively, these findings suggest that ectopic expression of Bcl-2 appeared to inhibit TSA-induced apoptosis by interfering with inhibition of Bcl-2 and caspase activation.

Bcl-2 Overexpression Inhibits Generation of Intracellular Reactive Oxygen Species and Blocks Adriamycin-induced Apoptosis in Bladder Cancer Cells

  • Kong, Chui-Ze;Zhang, Zhe
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.2
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    • pp.895-901
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    • 2013
  • Resistance to induction of apoptosis is a major obstacle for bladder cancer treatment. Bcl-2 is thought to be involved in anti-apoptotic signaling. In this study, we investigated the effect of Bcl-2 overexpression on apoptotic resistance and intracellular reactive oxygen species (ROS) generation in bladder cancer cells. A stable Bcl-2 overexpression cell line, BIU87-Bcl-2, was constructed from human bladder cancer cell line BIU87 by transfecting recombinant Bcl-2 [pcDNA3.1(+)-Bcl-2]. The sensitivity of transfected cells to adriamycin (ADR) was assessed by MTT assay. Apoptosis was examined by flow cytometry and acridine orange fluorescence staining. Intracellular ROS was determined using flow cytometry, and the activities of superoxide dismutase (SOD) and catalase (CAT) were also investigated by the xanthinoxidase and visible radiation methods using SOD and CAT detection kits. The susceptibility of BIU87-Bcl-2 cells to ADR treatment was significantly decreased as compared with control BIU87 cells. Enhanced expression of Bcl-2 inhibited intracellular ROS generation following ADR treatment. Moreover, the suppression of SOD and CAT activity induced by ADR treatment was blocked in the BIU87-Bcl-2 case but not in their parental cells. The overexpression of Bcl-2 renders human bladder cancer cells resistant to ADR-induced apoptosis and ROS might act as an important secondary messenger in this process.

Expressions of Apoptotic Genes (survivin, bcl-2, bax) and Clinical Relevance in Osteosarcoma (골육종에서 세포 사멸 관련 유전자 survivin, bcl-2, bax의 발현과 임상적 의의)

  • Kang, Hyun-Guy;Kim, Han-Soo;Lee, Mi-Ra;Seol, So-Mi;Oh, Joo-Han;Lee, Sang-Hoon;Kang, Gyeong-Hoon
    • The Journal of the Korean bone and joint tumor society
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    • v.11 no.2
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    • pp.118-125
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    • 2005
  • Purpose: The expression of apoptosis-related genes, such as survivin, bcl-2, and bax has been examined in the human osteosarcoma and then evaluated the correlation with clinical data of patients. Materials and Methods: Fifty human osteosarcoma specimens were established from incisional biopsy and examination of survivin, bcl-2, and bax by immunohistochemical study was performed. We investigated the correlation of survivin, bcl-2, bax and their two or three combined expressions with clinical data including the response of chemotherapy, local recurrence, distance metastasis, and oncologic outcome. Results: Survivin was showed in 26 cases (52%), bcl-2 in 23 cases (46%), and bax in 21 cases (42%) osteosarcoma. And coexpression of survivin and bcl-2 was showed in 19 cases (38%), survivin and bax in 13 cases (26%), bcl-2 and bax in 8 cases (16%), and all three expression was showed in 8 cases (16%). There was no correlation between their apoptosis related gene and histologic difference, the presence of local recurrence and distant metastasis. Whereas neoadjuvant chemotherapy response correlated with bcl-2 expression (P=0.04), and survivin and bcl-2 coexpression (P=0.044) with poor chemoresponse. The rate of died of disease was correlated with bcl-2 (P=0.001), survivin and bcl-2 coexpression (P=0.027) with bad outcome. Survival curves of bcl-2 (P=0.0075), survivin and bcl-2 (P=0.0012) was showed negative correlation in the Kaplan-Meier method. Conclusion: The apoptosis related gene expression was relatively high in osteosarcoma, bcl-2 expression was correlated with poor chemotherapy response and poor survival rate, but survivin was correlated with this oncologic outcome only in the bcl-2 coexpression. The examination of immunohistochemical stain of apoptosis related gene in osteosarcoma could be helpful in the judgment of osteosarcoma prognosis.

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Antisense bcl-2 Treatment in Human Lung Cancer Cell Lines (사람 폐암세포주에서의 bcl-2 안티센스 처리에 의한 효과)

  • 김선미;정자영;오호정;손여원
    • Toxicological Research
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    • v.18 no.4
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    • pp.411-416
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    • 2002
  • Apoptosis, or programmed cell death, is a genetically regulated pathway that is altered in many cancers. Overexpression of bcl-2 leads to resistance to apoptosis and promotes tumorigenesis. To determine the effect of bcl-2 antisense treatment in human lung cancer cell lines, a 20 mer full phosphorothioate oligonucleotide (ODN) targeted at the coding region of the bcl-2 mRNA was synthesized. Western blot analyses were used to examine bcl-2 protein level in five human non-small cell lung cancer (NSCLC) cell lines (NCI-H226, SK-MES-1 NCI-H358, NCI-H522 and NCI-Hl 299) and four human small cell lung cancer (SCLC) cell lines (NCI-H69, NCI-H4l7, HCC-2108 and SW2). Three out of five NSCLC (NCI-H226, SK-MES-1 and NCI-Hl 299) and all of SCLC cell lines expressed Bcl-2 protein. Treatment of these cell with antisense ODN for 48 hours reduced their viability and Bcl-2 protein level. As a conclusion, bcl-2 antisense treatment appears reduction of the Bcl-2 protein levels and cytotoxic effect including apoptosis in human lung cancer cell lines.

Effect of Bcl-2 on Apoptosis and Transcription Factor NF-κB Activation Induced by Adriamycin in Bladder Carcinoma BIU87 Cells

  • Zhang, Guo-Jun;Zhang, Zhe
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.4
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    • pp.2387-2391
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    • 2013
  • Resistance to apoptosis is a major obstacle preventing effective therapy for malignancies. Bcl-2 plays a significant role in inhibiting apoptosis. We reconstructed a stable human Bcl-2 transfected cell line, BIU87-Bcl-2, that was derived from the transfection of human bladder carcinoma cell line BIU87 with a plasmid vector containing recombinant Bcl-2 [pcDNA3.1(+)-Bcl-2]. A cell line transfected with the plasmid alone [pcDNA3.1(+)-neo] was also established as a control. BIU87 and BIU87-neo proved sensitive to adriamycin induced apoptosis, while BIU87-Bcl-2 was more resistant. In view of the growing evidence that NF-${\kappa}B$ may play an important role in regulating apoptosis, we determined whether Bcl-2 could modulate the activity of NF-${\kappa}B$ in bladder carcinoma cells. Stimulation of BIU87, BIU87-neo and BIU87-Bcl-2 with ADR resulted in an increase expression of NF-${\kappa}B$ (p<0.001). The expression of NF-${\kappa}B$ in BIU87-Bcl-2 was higher than in the other two cases, with a concomitant reduction in the $I{\kappa}B{\kappa}$ protein level. These results suggest that the overexpression of Bcl-2 renders human bladder carcinoma cells resistant to adriamycin-induced cytotoxicity and there is a link between Bcl-2 and the NF-${\kappa}B$ signaling pathway in the suppression of apoptosis.

Immunohistochemical study on the expression of bcl-2 protein during follicular development and atresia in the rat ovary (흰쥐 난포의 성장과 퇴화에 따른 bcl-2 단백질 발현에 관한 면역조직화학적 연구)

  • Koh, Phil-ok;Jeong, Sung-yoon;Cho, Gyeong-jae;Choi, Wan-sung;Kwak, Soo-dong
    • Korean Journal of Veterinary Research
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    • v.39 no.1
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    • pp.27-33
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    • 1999
  • In the mammalian ovary, follicular development and atresia continuously occur during the reproductive cycles. Follicular atresia occurs through granulosa cell apoptosis. Apoptosis is known as the physiological cell death, which is regulated by bcl-2 gene family. In the bcl-2 gene family, bcl-2 and bcl-xLong are known as inhibitors of apoptosis, whereas bax and bcl-xShort are known as inducer of apoptosis. We thought that bcl-2 protein is associated with follicular development and atresia. But it is not known that the distribution of cells containing bcl-2 protein during follicular development and atresia. Therefore, to examine the distribution of cells with bcl-2 protein during ovarian follicular development and atresia, the immunohistochemistry was used in the rat ovary. Bcl-2 immunoreactivity was localized in the interstitial cells, theca externa cells and granulosa cells around of antrum. All positive signals were observed in the cytoplasm of these cells. Positive signals were strongly observed in the interstitial and theca externa cells of growing antral follicles. While, positive signals were weakly observed in these cells from atretic antral follicles. Positive signals were very weakly observed in the granulosa cells of growing and atretic antral follicles. According to these data, we suggested that bcl-2 proteins which were strongly expressed in the interstitial cells and theca externa cells of growing antral follicles inhibit follicular atresia. And we purposed that bcl-2 proteins regulated follicular development and atresia through the action of bcl-2 gene family.

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Apoptosis and Bcl-2 in Astrocytic Tumors (성상교세포종에서 Apoptosis와 Bcl-2 발현)

  • Jang, Yeon Gyoe;Whang, Kum;Hong, Soon-Won
    • Journal of Korean Neurosurgical Society
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    • v.29 no.4
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    • pp.485-490
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    • 2000
  • Objective : To study the expression of apoptosis and bcl-2 in the astrocytic tumors. Patients and Methods : A total of thirty-eight astrocytomas(9 cases in low grade astrocytoma, 12 cases in anaplastic astrocytoma and 17 cases in glioblastoma) are included in this study. Immunohistochemical stain for bcl-2 using monoclonal antibody, in situ end labelling technique for apoptosis were used. Results : The malignant group(anaplastic astrocytoma and glioblastoma) showed significantly higher apoptosis positive index(PI) compared to the benign group(low grade astrocytoma)(1.35 vs 0.14). However apoptosis PI and bcl-2 PI were not significantly different among three groups. Correlation between apoptosis PI and bcl-2 PI was not statistically significant(p=0.58). Conclusion : This result suggest that apoptosis PI and bcl-2 PI are not related the degree of malignancy in astrocytic neoplasm, but apoptosis PI in malignant group was higher possibly due to greater DNA damage.

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