Differential polyamine analogue effects in four human breast cancer cell lines

Holst, C. Martina; Frydman, Benjamiǹ; Marton, Laurence J.; Oredsson, Stina

doi:10.1016/j.tox.2006.03.009

Cited by 22 publications

(34 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Also, the recent study examines that polyamine depletion inhibited migration [15] and delayed cell attachment to ECM proteins by disrupting the cytoskeleton [22]. Previous studies have shown that increased spm concentrations in tumor tissues are correlated with cancer progression and that restriction of polyamine availability inhibits tumor growth [13]. However, the present results show that polyamines, especially spm, suppressed MCF-7 22 생명과학회지 2012, Vol.…”

Section: Discussioncontrasting

confidence: 55%

Modulation of Adhesion Proteins Integrin β1 and FAK, and Cytoskeletal Protein Actin by Spermine in MCF-7 Cells

Jee¹,

Kim²

2012

Journal of Life Science

View full text Add to dashboard Cite

Polyamines are essential for cell growth and differentiation; however their precise roles are unclear yet. In the present study, the cytotoxic effect of spermine (spm) on MCF-7 cells was investigated. In the MTT assay of MCF-7 cells treated with spm, cell viability was significantly decreased in a time-and dose-dependent manner. Cell viability measurement was confirmed by trypan blue staining. FACS analysis shows that sub-G1 was increased in a time-and dose-dependent manner too. When the cells were treated with spm, cells started to show morphological changes within 2 hrs. The expression of adhesion proteins (FAK and integrin β1), and cytoskeletal protein (actin) was checked by Western blotting analysis. Integrin β1 levels were slightly decreased, and FAK and actin levels were rapidly decreased with spm treatment. In confocal laser scanning microscopy, the distribution of actin did not change but the expression decreased in a dose-dependent manner with spm treatment. FAK was evenly distributed under the plasma membrane in the untreated control. However, at 10 μM spm FAK seemed to move toward the cell nucleus. Integrin β1, which was mainly found in the focal point of the plasma membrane in the untreated control, dispersed through the entire plasma membrane in spm treatment. The present results indicate that cytotoxic effects of spm are triggered by the disruption of adhesion proteins and cytoskeletal protein. IntroductionPolyamines such as putrescine (put), spermidine (spd), and spermine (spm) are small, flexible molecules, which bind to nucleic acids and proteins and thus affect their conformation and biological activity [25]. Polyamines are important multifunctional cellular components and are considered mediators of cell growth and division. Recently, polyamines have also been known to be implicated in cell death. It appears that polyamines are bivalent regulators of cellular functions, promoting proliferation or cell death depending on the cell type and on environmental signals [12,18]. Among polyamines, spm was most effective in inhibiting cancer cell growth. The cytotoxicity of spm has been suggested by the production of H2O2 and aldehyde(s) from spm in the presence of amine oxidase [1,2].Polyamines are also essential for the normal attachment of cells to the extracellular matrix (ECM), which explains at least some of the reliance of cell migration and the organization of the cytoskeleton on normal polyamine levels [22]. The migration of cells depends on their ability to make and break attachments to the ECM. The ECM controls cells through signals via a family of cell surface receptors called integrins [10]. The malignancy of a tumor is associated with its ability to undergo migration and metastasis. Metastases form after a series of sequential, interlinked steps involving a variety of adhesive interactions between cancer cells and host tissues [7]. The mechanism that plays a role in the cytotoxic properties of polyamine may be related to the down-regulation of integrin-associated signaling. Integrin famil...

show abstract

Section: Discussioncontrasting

confidence: 55%

Modulation of Adhesion Proteins Integrin β1 and FAK, and Cytoskeletal Protein Actin by Spermine in MCF-7 Cells

Jee¹,

Kim²

2012

Journal of Life Science

View full text Add to dashboard Cite

show abstract

“…Cell death was monitored by flow cytometry as the appearance of a sub-G 1 region in the DNA histogram [22]. A rapid induction of cell death was observed in L56Br-C1 cells where the polyamine pools were lowest.…”

Section: Effect Of Denspm Treatment On Polyamine Pools In Relation Tomentioning

confidence: 99%

Inhibition of cell proliferation and induction of apoptosis by N1,N11-diethylnorspermine-induced polyamine pool reduction

Oredsson

Alm

Dahlberg

et al. 2007

Biochemical Society Transactions

View full text Add to dashboard Cite

Reduction of cellular polyamine pools results in inhibition of cell proliferation and sometimes in induction of cell death. Reduction of cellular polyamine pools can be achieved by several strategies involving all the mechanisms of polyamine homoeostasis, i.e. biosynthesis, catabolism and transport across the cell membrane. In the present paper, we concentrate on results achieved using the polyamine analogue DENSPM (N(1),N(11)-diethylnorspermine) on different cell lines. We discuss polyamine levels in DENSPM-treated cells in relation to effects on cell cycle kinetics and induction of apoptosis. To really understand the role of polyamines in cell cycle regulation and apoptosis, we believe it is now time to go through the vast polyamine literature in a meta-analysis-based manner. This short review does not claim to be such a study, but it is our hope to stimulate such studies in the polyamine field. Such work is especially important from the viewpoint of introducing drugs that affect polyamine homoeostasis in the treatment of various diseases such as cancer.

show abstract

“…DENSPM-induced cell death was shown to be caspase dependent as it was blocked by Z.VAD.FMK, a general caspase inhibitor. In addition, using different methods to study cytotoxicity, we found that DENSPM treatment, and also treatment with other polyamine analogues, affected the mitochondria in all cell lines presumably by increasing the rate of respiration [11,26].…”

Section: Discussionmentioning

confidence: 99%

“…The human ductal carcinoma breast cancer cell line HCC1937 [25] was cultured in MEM a-medium supplemented with 10% heat-inactivated FCS, nonessential amino acids at standard concentrations, epidermal growth factor (20 ng/ml), insulin (10 mg/ml), penicillin (50 U/ml) and streptomycin (50 mg/ml). The human breast cancer cell line L56Br-C1 [11,24,26] was cultured in RPMI 1640 medium supplemented with 10% heatinactivated FCS, nonessential amino acids at standard concentrations, insulin (10 mg/ml), penicillin (50 U/ml) and streptomycin (50 mg/ml). Cells were seeded in the absence or presence of 10 mmol/l DENSPM.…”

Section: Cell Culturementioning

confidence: 99%

Molecular mechanisms underlying N 1, N 11-diethylnorspermine-induced apoptosis in a human breast cancer cell line

et al. 2008

Self Cite

View full text Add to dashboard Cite

Polyamine analogue treatment results in growth inhibition and sometimes in cell death. Therefore, polyamine analogues are considered in the treatment of cancer; however, the cellular properties that govern sensitivity are not known. The objective of this study was to elucidate molecular mechanisms behind apoptosis induced by the polyamine analogue N, N-diethylnorspermine (DENSPM). Four different breast cancer cell lines were treated with DENSPM. Cell death was evaluated with flow cytometry and a caspase 3 assay. The levels of a number of proapoptotic and antiapoptotic proteins in subcellular compartments were evaluated with western blot. In the most sensitive cell line, DENSPM treatment induced the release of cytochrome c from mitochondria, resulting in activation of caspase 3 but without decreasing the mitochondrial transmembrane potential. However, in the three other cell lines DENSPM treatment did not induce extensive cell death. This is partly explained by the high levels of antiapoptotic proteins Bcl-2 and Bad and low levels of proapoptotic proteins Bax and procaspase 3 in these three cell lines. The results are also partly explained by the degree of activation of the catabolic enzyme spermidine/spermine-N-acetyltransferase and polyamine pool reduction achieved by DENSPM treatment. Our results show that the protein profile of proapoptotic and antiapoptotic proteins may contribute to the outcome to treatment with the polyamine analogue DENSPM. The results also indicate that it should be possible to find molecular markers for sensitivity to DENSPM that could be used in the clinic to predict sensitivity to a polyamine analogue.

show abstract

Differential polyamine analogue effects in four human breast cancer cell lines

Cited by 22 publications

References 34 publications

Modulation of Adhesion Proteins Integrin β1 and FAK, and Cytoskeletal Protein Actin by Spermine in MCF-7 Cells

Modulation of Adhesion Proteins Integrin β1 and FAK, and Cytoskeletal Protein Actin by Spermine in MCF-7 Cells

Inhibition of cell proliferation and induction of apoptosis by N1,N11-diethylnorspermine-induced polyamine pool reduction

Molecular mechanisms underlying N 1, N 11-diethylnorspermine-induced apoptosis in a human breast cancer cell line

Contact Info

Product

Resources

About