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Tin reorganization and accumulation of G-actin in apoptotic bodies [81]. In light of these findings, it also seems meaningful that G-actin functions as an inhibitor of DNase I [82-84] until the proteolyticLitwiniec et al. Cancer Cell International 2013, 13:9 http://www.cancerci.com/content/13/1/Page 17 ofcleavage in advanced stages of apoptosis. Furthermore, inhibition of the proteolytic cleavage of actin results in the suppression of DNA fragmentation in etoposidetreated cells, and mutation of the cleavage-site may actually lead to cellular transformation [82,85]. The presence of actin was shown to be crucial for transduction of necrosis-related signaling into mitochondria [86].Conclusions In conclusion, although the occurrence of a stable senescence program in single etoposide-exposed cells could not be ruled out, e.g. as a result of mitotic block in cells with failed cytokinesis [87], a great deal of caution should be advised when interpreting a general response to etoposide in A549 cell population as a senescence phenomenon. In this study, SAHF, which are believed to contribute to cell-cycle exit via suppression of proliferation-driven genes, were observed only exceptionally. Moreover, although G2/M arrest occurred, it was accompanied by a concomitantly increasing fraction of polyploid TUNEL-positive cells, which, along with the lack of nuclear G-actin accumulation seems to exclude a stable G0/G1 arrest of cells with unreduced DNA content. We suggest that a delicate balance between selfrenewal and senescence in A549 cells may be affected as a result of impairments in two important senescence pathways, i.e. via p53 and pRb. This, in turn, may be a consequence of the genetic background of A549 cell line, i.e. homozygous deletion of the Ink4b/Arf/Ink4a locus. In agreement with these presumptions, it has PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/9638577 been previously documented that p53 journal.pone.0167038 and/or p16Ink4a defects may contribute to the proneness of some lung cancer cells to senescence escape [27]. In our microscopic observations we were also unable to show significant induction of either p21Waf1/Cip1/Sdi1 or prominent SAFH formation, supporting the suggestion that some features of senescence may appear in this situation independently of a cell cycle arrest and/or secondarily, as a consequence Tert-butyl 2-(chloromethyl)pyrrolidine-1-carboxylate of abnormal mitosis/polyploidization. Aberrant regulation of cyclin D1 may also contribute to this phenotype, which requires further studies. Thus, the response of the A549 population to etoposide may be described PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/9544797 as heterogeneous, demonstrating not only some features of cell death, but also broad polyploidization events typical of a pre-senescent stage, as well as the senescence-like phenotype manifesting itself mainly as a kind of metabolic shift, resembling autophagic demolition of the cellular content. This seems particularly interesting in light of recent findings suggesting the involvement of autophagy in the development of morphological symptoms at a pre-senescence stage [42,48,88,89], Boc-D-Lys-OH but the precise role of this program is yet to be determined. Besides that, pre-senescent tetraploid/ polyploid cells were shown to coordinate DNA-damageresponse, self-renewal and senescence signalling pathways [42,90,91], constituting a potential source of extended-life cells or, in cancer cell populations, cancer stem cells [37,38]. Apart from that, the morphological senescence-like alterations observed by us were unaccompanied by a stable cell cycle arrest. Last but not least, here we present preliminary mor.