The Bcl-2/Bax and Ras/Raf/MEK/ERK signaling pathways: implications in pediatric leukemia pathogenesis and new prospects for therapeutic approaches

Vitagliano, Orsola; Addeo, Raffaele; D’Angelo, Velia; Indolfi, Cristiana; Indolfi, Paolo; Casale, Fiorina

doi:10.1586/17474086.2013.827415

Cited by 54 publications

(49 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cancer cells often express elevated levels of antiapoptotic members of Bcl-2 family, so as to obtain survival and proliferation advantage. Bcl-2 protein is the prototype of this family, which targets intracellular organelles such as the endoplasmic reticulum, outer mitochondrial, and nuclear membranes [18]. Mcl-1 act as an apical molecule in apoptosis control, promoting cell survival by interfering at an early stage in a cascade of events leading to release of cytochrome c from mitochondria.…”

Section: Discussionmentioning

confidence: 99%

Norcantharidin induces growth inhibition and apoptosis of glioma cells by blocking the Raf/MEK/ERK pathway

Zheng

Song

et al. 2014

World J Surg Onc

View full text Add to dashboard Cite

BackgroundMalignant gliomas represent the most common primary brain tumors. The prognosis of patients with malignant gliomas is poor in spite of current intensive therapy and novel therapeutic modalities are needed. Here we report that norcantharidin is effective in growth inhibition of glioma cell lines in vitro.MethodsGlioma cell lines (U87 and C6) were treated with norcantharidin. The effects of norcantharidin on the proliferation and apoptosis of glioma cells were measured by 3-[4,5-dimethylthiazol-2-thiazolyl]-2,5-diphenyl-tetrazolium bromide (MTT) assay and flow cytometry. Western blotting was employed to determine the signaling pathway changes.ResultsThe results showed that norcantharidin effectively inhibited cell growth and induced apoptosis in glioma cells, which was concurrent with inhibition of the expression of phospho-MEK and phospho-ERK. Furthermore, the expression anti-apoptotic proteins Bcl-2 and Mcl-1 significantly reduced, but no changes in Bcl-xL and Bax.ConclusionsOur findings demonstrate that norcantharidin is effective for growth inhibition of glioma cell lines and suggest that norcantharidin may be a new therapeutic option for patients with glioma.

show abstract

Section: Discussionmentioning

confidence: 99%

Norcantharidin induces growth inhibition and apoptosis of glioma cells by blocking the Raf/MEK/ERK pathway

Zheng

Song

et al. 2014

World J Surg Onc

View full text Add to dashboard Cite

show abstract

“…By binding to insulin-like growth factor 1 receptor (IGF1R), a tyrosine kinase cell-surface receptor, its tyrosine kinase activity is activated to regulate cell proliferation and cell survival through intracellular networks [16]. The PI3K-AKT signaling pathway and MAPK pathway are the key downstream networks which have been validated as deregulating in hematologic malignancies [16,17,18]. In addition, mounting evidence showed the expression of IGF system has an impact on the initiation and progression of cancers.…”

Section: Introductionmentioning

confidence: 99%

Interaction Between IGF1 Polymorphisms and the Risk of Acute Lymphoblastic Leukemia in Chinese Children

Lu¹,

Wang²,

He³

et al. 2015

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: IGF1 is a key regulator in cell proliferation and apoptosis, and the 3' un-translated region (3'UTR) of the gene plays an important role in gene expression. For the first time, we explored the relationship between polymorphisms in the IGF1 3'UTR region and the risk of childhood acute lymphoblastic leukemia (ALL). Methods: Questionnaires were applied to collect epidemiological data. The genotypes of IGF1 polymorphisms were tested in a population of 744 ALL patients and 1088 cancer-free controls utilizing Taqman. Cell functional studies included real-time PCR, cell culture and transfection and luciferase assays. Results: We found that rs6214 homozygous AA genotype and rs6218 homozygous CC genotype were significantly associated with increased risk of childhood ALL. In addition, rs6218 CC genotype was associated with increased level of IGF1 mRNA in bone marrow, and the mutation in rs6218 led to aberrant binding capacity of hsa-miR-603 and hsa-miR-3941 in the 3'UTR of IGF1. Conclusion: Polymorphisms of rs6214 and rs6218 in the 3'UTR of IGF1 are associated with childhood ALL susceptibility, and the polymorphism of rs6218 is related with IGF1 expression at mRNA level.

show abstract

“…As a model target gene, BCL-2 gene expression was chosen for silencing, as this gene was found overexpressed 13,14 in most of the leukemic cell types (for a review see refs. [15][16][17][18] ). In this study we found that antisense ODNs against the gene encoding the B-cell lymphoma 2 protein (Bcl-2) encapsulated into a liposomal envelope named L-cL could be used as genotype-specific drugs that delay tumor growth in vivo.…”

Section: Introductionmentioning

confidence: 99%

Liposome-coated lipoplex–based carrier for antisense oligonucleotides

Wyrozumska

Meissner

Toporkiewicz

et al. 2014

Cancer Biology & Therapy

View full text Add to dashboard Cite

fluorescent protein; HPC, hydrogenated egg phosphatidylcholine); pDNA, plasmid DNA; PE/PC, phosphatidylethanolamine and phosphatidylcholine liposomes; siRNA, small interferingRNA TGI, tumor growth inhibition.The chemical nature of genetic drugs (e.g. antisense oligonucleotides, siRNA, vectors) requires a suitable carrier system to protect them from enzymatic degradation without changing their properties and enable efficient delivery into target cells. Lipid vectors for nucleic acid delivery that have been widely investigated for years can be very effective. As the majority of attempts made in the field of cancer gene therapy have focused on solid tumors, while blood cancer cells have attracted less attention, the latter became the subject of our investigation. The lipid carrier proposed here is based on liposomes constructed by others but the lipid composition is original. A liposome-coated lipoplex (L-cL) consists of a core arising from complexation of positively charged lipid and negatively charged oligodeoxynucleotide (ODN) or plasmid DNA coated by a neutral or anionic lipid bilayer. Moreover, our lipid vector demonstrates size stability and is able to retain a high content of enclosed plasmid DNA or antisense oligodeoxynucleotides (asODNs). Observed transfection efficacies of the tested preparation using a plasmid coding for fluorescent protein were up to 60-85% of examined leukemia cells (Jurkat T and HL-60 lines) in the absence or the presence of serum. When BCL-2 asODN was encapsulated in the L-cL, specific silencing of this gene product at both the mRNA and protein level and also a markedly decreased cell survival rate were observed in vitro. Moreover, biodistribution analysis in mice indicates prolonged circulation characteristic for PEG-modified liposomal carriers. Experiments on tumor-engrafted animals indicate substantial inhibition of tumor growth.

show abstract

The Bcl-2/Bax and Ras/Raf/MEK/ERK signaling pathways: implications in pediatric leukemia pathogenesis and new prospects for therapeutic approaches

Cited by 54 publications

References 40 publications

Norcantharidin induces growth inhibition and apoptosis of glioma cells by blocking the Raf/MEK/ERK pathway

Norcantharidin induces growth inhibition and apoptosis of glioma cells by blocking the Raf/MEK/ERK pathway

Interaction Between IGF1 Polymorphisms and the Risk of Acute Lymphoblastic Leukemia in Chinese Children

Liposome-coated lipoplex–based carrier for antisense oligonucleotides

Contact Info

Product

Resources

About