Bcl-xL blocks high dose doxorubicin-induced apoptosis but not low dose doxorubicin-induced cell death through mitotic catastrophe

Park, Seok Soon; Kim, Mi Ae; Eom, Young-Woo; Choi, Kyeong Sook

doi:10.1016/j.bbrc.2007.09.037

Cited by 27 publications

(23 citation statements)

References 26 publications

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“…Many studies using different cell lines showed that low concentrations of DOX promote cell senescence or mitotic catastrophe, while higher doses induce apoptosis [26][27][28][29]. In the present study, H1299 cells showed cell shape changes following DOX treatment.…”

Section: Discussionsupporting

confidence: 52%

The role of exportin 6 in cytoskeletal-mediated cell death and cell adhesion in human non-small-cell lung carcinoma cells following doxorubicin treatment

Izdebska

Gagat²,

Grzanka³

et al. 2014

Folia Histochem Cytobiol.

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Abstract:The actin cytoskeleton plays an important role in various cellular processes. The different forms of actin (G-actin and F-actin) participate in the organization of nuclear structure and its functions. The structure of the actin cytoskeleton is controlled by proteins involved in the translocation of actin between cytoplasm and the nucleus. In this study, we used siRNA method to investigate the role of exportin 6 in the switching between nuclear and cytoplasmic F-actin pools in H1299 cells treated with no, 1.0 or 2.5 µM doxorubicin. We showed that silencing of exportin 6 expression changed the response of H1299 to doxorubicin. Here, we observed increased population of cells affected by doxorubicin-induced necrotic cell death. Furthermore, fluorescence studies showed that downregulation of exportin 6 exerted profound DOX-induced changes in the F-actin cytoskeleton architecture. The F-actin cytoskeleton was seen in the form of small fibers or aggregates after doxorubicin treatment. Additionally, some cells lost cell adhesion properties. Downregulation of exportin 6 influenced also transcriptional activity of the cells. In cells transfected with nontargeting siRNA, we observed a higher level of 5'-fluorouridine fluorescence than in cells with silenced exportin 6 expression. In conclusion, we showed that downregulation of exportin 6 induced necrotic cell death. Moreover, the observed alterations of cell adhesion suggest the key role of cytoplasmic F-actin in maintaining intercellular junctional complexes and/or focal adhesion properties and the importance of the balance between nuclear and cytoplasmic F-actin pools.

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Section: Discussionsupporting

confidence: 52%

The role of exportin 6 in cytoskeletal-mediated cell death and cell adhesion in human non-small-cell lung carcinoma cells following doxorubicin treatment

Izdebska

Gagat²,

Grzanka³

et al. 2014

Folia Histochem Cytobiol.

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“…Although low doses of such agents are still able to induce an immediate interphase death of some tumour cells, most cells become arrested in the G1-S or G2-M boundaries. Because doxorubicin administration has been reported to induce different modes of cell death dependent on the dosage Park et al, 2005;Park et al, 2007), the susceptibility of 14-3-3s-knockout HCT116 cells to MC upon treatment with low (600 nM) or high (2 mM) doxorubicin doses was investigated. As expected, changes in nuclear morphology and TUNEL-positivity were different and dose-dependent.…”

Section: Cells That Undergo MC Trigger P53-dependent Apoptosismentioning

confidence: 99%

Chromosomal breaks during mitotic catastrophe trigger γH2AX–ATM–p53-mediated apoptosis

Imreh

Norberg

Imreh

et al. 2011

Journal of Cell Science

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) relating to the article 'Chromosomal breaks during mitotic catastrophe trigger γH2AX-ATM-p53-mediated apoptosis' by Gabriela Imreh, Helin Vakifahmetoglu Norberg, Stefan Imreh and Boris Zhivotovsky. J. Cell Sci. 2011Sci. 124, 2951Sci. -2963Sci. (doi: 10.1242).Concerns were raised regarding some of the data in Fig. 1A of the above-named paper. An investigation carried out by Karolinska Institutet concluded that no wrongdoing had occurred, and that no further action was required. An in-house review of the original data by Journal of Cell Science reached a similar conclusion.Journal of Cell Science is publishing this Note to alert readers that the concerns raised about this paper have been resolved. This course of action follows the advice set out by COPE (Committee on Publication Ethics), of which Journal of Cell Science is a member. Concerns have been raised regarding some of the data in Fig. 1A of the above-named paper. Journal of Cell Science is publishing this note to make readers aware of this issue, and we will provide further information once the issue has been resolved. 3419This course of action follows the advice set out by COPE (Committee on Publication Ethics), of which Journal of Cell Science is a member. There was an error published in J. Cell Sci. 124, 2951-2963. 1979In Fig. 4C, the blot representing pATM was inadvertently duplicated as representing G3PDH. The G3PDH western blot has been replaced with the correct image in the figure shown below. There are no changes to the figure legend, which is accurate. This error does not affect the conclusions of the study.The authors apologise to the readers for any confusion that this error might have caused. Fig. 4. Increased γH2AX level during MC leads to cell death. Untreated or doxorubicin (600 nM)-treated 14-3-3σ-knockout HCT116 cells were cultured and harvested at indicated time points and analysed by western blot (50 μg), comet assay and immunostaining using antibodies directed against γH2AX (green). Blots were reprobed for G3PDH to confirm an equal loading of the samples. The co-staining of nuclei was performed using Hoechst 33342 (white). (A,B) Representative confocal images showing nuclear morphology and γH2AX staining in 14-3-3σ-knockout HCT116 (A) or wild-type HCT116 (B) cells after treatment for indicated time. (C) 14-3-3σ-knockout HCT116 cells were treated for 9 hours with doxorubicin after which the culture medium was replaced and cells were grown for an additional 24, 48 and 72 hours. Immunoblots of p53, phosphorylated ATM and γH2AX are shown. (D) Doxorubicin-induced DNA damage measured by alkaline comet assay. Cells were analysed by fluorescence microscopy and scored according to tail moment. Error bars represent the mean of three independent experiments±s.e.m. Scale bar: 20 μm. Science (2016Science ( ) 129, 1950Science ( doi:10.1242 © 2016. Published by The Company of Biologists Ltd | Journal of Cell Journal of Cell ScienceChromosomal breaks during mitotic catastrophe trigger cH2AX-ATM-p53-mediated apoptosis Summary Although the cause...

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“…Anticancer drugs, including ADM, frequently act by inducing apoptosis of hepatoma cells [13], but recent studies have indicated that apoptosis may not be the primary mechanism of cell death [14][15][16]. Autophagy, also designed as type II programmed cell death, is a physiological mechanism that involves the sequestration of cytoplasm and intracellular organelles into membrane vacuoles called autophagosomes, and results in their eventual enzymatic degradation [17].…”

Section: Discussionmentioning

confidence: 99%

Alterations of cellular organelles in human liver-derived hepatoma G2 cells induced by adriamycin

Qian

Yang²

2009

Anti-Cancer Drugs

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Adriamycin (ADM) is a commonly used chemotherapeutic drug in the treatment of hepatocellular carcinoma. However, the mechanisms involved in ADM-induced cell death and the molecular basis of ADM resistance are still unclear. To observe the early events that occurred in hepatoma cells in response to ADM, we investigated the alterations of morphology and subcellular distributions of cellular organelles in human liver-derived hepatoma G2 (HepG2) cells after ADM treatment. HepG2 cells were exposed to different doses of ADM for up to 60 h. Cytotoxicity occurred 24 h after 0.05 microg/ml ADM application, and remaining living cells showed irregular shapes but continued to multiply. Some cellular organelles altered their subcellular distribution or morphology after ADM treatment, including mitochondria, autophagic vacuoles, and Golgi apparatus. Immunoblotting with anti-LC3 antibody showed the upregulation of LC3-II protein, confirming that ADM leads to the induction of autophagy in HepG2 cells. Our findings suggest that among most of the cellular organelles, mitochondria and autophagic vacuoles were involved in the early ADM response, and may contribute to ADM-induced HepG2 cell death.

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Bcl-xL blocks high dose doxorubicin-induced apoptosis but not low dose doxorubicin-induced cell death through mitotic catastrophe

Cited by 27 publications

References 26 publications

The role of exportin 6 in cytoskeletal-mediated cell death and cell adhesion in human non-small-cell lung carcinoma cells following doxorubicin treatment

The role of exportin 6 in cytoskeletal-mediated cell death and cell adhesion in human non-small-cell lung carcinoma cells following doxorubicin treatment

Chromosomal breaks during mitotic catastrophe trigger γH2AX–ATM–p53-mediated apoptosis

Alterations of cellular organelles in human liver-derived hepatoma G2 cells induced by adriamycin

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