In vitro modulation of Bcl-2 levels in small cell lung cancer cells: effects on cell viability

Santos, Adriana O.; Pereira, João; Lima, Maria C. Pedroso de; Simões, Sérgio; Moreira, João Nuno

doi:10.1590/s0100-879x2010007500099

Cited by 6 publications

(3 citation statements)

References 36 publications

(39 reference statements)

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“…BCL-2, Bcl-XL, Bcl-w) and the other with pro-apoptotic (i.e.Bax, Bim, Bid) properties30, 31. BCL-2 predominantly localized in mitochondria which is the central coordinator of both intracelluar and extracellular signals mediating caspase-dependent and caspase-independent cell death32-34. Recently, it has been reported that induction of mitochondrial apoptosis requires the involvement of BCL-235, 36.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-7 Inhibits the Growth of Human Non-Small Cell Lung Cancer A549 Cells through Targeting BCL-2

Xiong¹,

Zheng²,

Jiang³

et al. 2011

Int. J. Biol. Sci.

173

125

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MicroRNAs(miRNAs) are emerging as important regulators in tumorigenesis. Increasing evidences have indicated microRNA-7(miR-7) to be a potential tumor suppressor in several human cancers. However, only a limited number of target genes have been identified so far and its biological function in Non-Small Cell Lung Cancer (NSCLC) remains to be further elucidated. In the present study, we observed a reduction of miR-7 level in NSCLC cell lines. Overexpression of miR-7 not only suppressed NSCLC A549 cells proliferation, induced cell apoptosis and inhibited cell migration in vitro, but also reduced tumorigenicity in vivo. Bioinformatics predictions revealed a potential binding site of miR-7 on 3'UTR of BCL-2 and it was further confirmed by luciferase assay. Moreover, subsequent experiments showed that BCL-2 was downregulated by miR-7 at both transcriptional and translational levels. These results suggest that miR-7 regulates the expression of BCL-2 through direct 3'UTR interactions. Therefore, we postulate BCL-2 to be a novel target possibly involved in miR-7-mediated growth suppression and apoptosis of A549 cells. These findings may provide a basic rationale for the use of miR-7 in the treatment of NSCLC.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-7 Inhibits the Growth of Human Non-Small Cell Lung Cancer A549 Cells through Targeting BCL-2

Xiong¹,

Zheng²,

Jiang³

et al. 2011

Int. J. Biol. Sci.

173

125

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“…The observation that Bcl-2 expression was elevated in primary SCLC, in comparison with normal lung tissue further supports this model, in view of the overexpression of p110-a. Importantly, the Bcl-2 family of proteins has been previously shown to play a crucial role in the survival of SCLC cell lines in vitro and in vivo (5,(22)(23)(24)(25)(26). The p110-a inhibitors induced increases in both SCLC apoptosis and autophagy, which is consistent with Bcl-2 family proteins being a target of p110-a.…”

Section: Discussionmentioning

confidence: 99%

Targeting the Phosphoinositide 3-Kinase p110-α Isoform Impairs Cell Proliferation, Survival, and Tumor Growth in Small Cell Lung Cancer

Wojtalla

Fischer

Kotelevets

et al. 2013

Clinical Cancer Research

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Purpose: The phosphoinositide 3-kinase (PI3K) pathway is fundamental for cell proliferation and survival and is frequently altered and activated in neoplasia, including carcinomas of the lung. In this study, we investigated the potential of targeting the catalytic class I A PI3K isoforms in small cell lung cancer (SCLC), which is the most aggressive of all lung cancer types.Experimental Design: The expression of PI3K isoforms in patient specimens was analyzed. The effects on SCLC cell survival and downstream signaling were determined following PI3K isoform inhibition by selective inhibitors or downregulation by siRNA.Results: Overexpression of the PI3K isoforms p110-a and p110-b and the antiapoptotic protein Bcl-2 was shown by immunohistochemistry in primary SCLC tissue samples. Targeting the PI3K p110-a with RNA interference or selective pharmacologic inhibitors resulted in strongly affected cell proliferation of SCLC cells in vitro and in vivo, whereas targeting p110-b was less effective. Inhibition of p110-a also resulted in increased apoptosis and autophagy, which was accompanied by decreased phosphorylation of Akt and components of the mTOR pathway, such as the ribosomal S6 protein, and the eukaryotic translation initiation factor 4E-binding protein 1. A DNA microarray analysis revealed that p110-a inhibition profoundly affected the balance of pro-and antiapoptotic Bcl-2 family proteins. Finally, p110-a inhibition led to impaired SCLC tumor formation and vascularization in vivo.Conclusion: Together our data show the key involvement of the PI3K isoform p110-a in the regulation of multiple tumor-promoting processes in SCLC.

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“…(2) The presence of associated diseases, such as rhinitis (symptoms are present in 90% of cases), gastroesophageal Sleep 5 [16][17][18][19][20] Physiology, exercise, and rehabilitation 12 [21][22][23][24][25][26][27][28][29][30][31][32] COPD 8 [33][34][35][36][37][38][39][40] Pathology 3 [41][42][43] CT 2 [44][45] Occupational medicine 1 46 Pulmonary thromboembolism 2 [47][48] Pulmonary hypertension 3 [49][50][51] Lung cancer 3 [52][53][54] Smoking 2 [55][56] Evaluation of articles on pulmonology published in Brazilian In their study involving patients with severe OSAS, Neves et al found that the use of sildenafil worsens OSAS, as well as causing deleterious cardiovascular effects because of the increased parasympathetic tone and affecting the HR variability. (19) Pires et al, in a study of drivers engaged in night shift work, contradicted the notion that the sleep pattern of older individuals is more negatively affected than that of younger individuals.…”

Section: Asthmamentioning

confidence: 99%

Avaliação dos artigos de pneumologia publicados em periódicos Brasileiros além do Jornal Brasileiro de Pneumologia

Baldi

Carvalho

2011

J. bras. pneumol.

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In Brazil, research on pulmonology has become increasingly more visible in recent years. In addition to the Brazilian Journal of Pulmonology, other journals have contributed to that by publishing relevant articles in this area. The objective of this article was to briefly report the most relevant studies on pulmonology that were published in other important Brazilian journals between 2009 and 2010. Altogether, there were 56 articles related to the various subareas that compose the field of respiratory diseases.Keywords: Pulmonary medicine; Research; Brazil. ResumoA pesquisa em pneumologia no Brasil tem apresentado progressivo destaque nos últimos anos e, além do Jornal Brasileiro de Pneumologia, outros periódicos têm contribuído com a publicação de manuscritos relevantes nessa área. Esse artigo teve por objetivo descrever resumidamente os principais trabalhos publicados no biênio 2009-2010 em pneumologia em outros importantes periódicos nacionais. Foram publicados 56 artigos das diferentes subáreas das doenças respiratórias.Descritores: Pneumologia; Pesquisa; Brasil.* Study carried out at

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In vitro modulation of Bcl-2 levels in small cell lung cancer cells: effects on cell viability

Cited by 6 publications

References 36 publications

MicroRNA-7 Inhibits the Growth of Human Non-Small Cell Lung Cancer A549 Cells through Targeting BCL-2

MicroRNA-7 Inhibits the Growth of Human Non-Small Cell Lung Cancer A549 Cells through Targeting BCL-2

Targeting the Phosphoinositide 3-Kinase p110-α Isoform Impairs Cell Proliferation, Survival, and Tumor Growth in Small Cell Lung Cancer

Avaliação dos artigos de pneumologia publicados em periódicos Brasileiros além do Jornal Brasileiro de Pneumologia

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