Interferon-alpha suppresses proliferation of chronic myelogenous leukemia cells K562 by extending cell cycle S-phase without inducing apoptosis

Grebeňová, Dana; Kuželová, Kateřina; Fuchs, Ota; Halada, Petr; Havlicek,; Marinov, Iuri; Hrkal, Zbyněk

doi:10.1016/j.bcmd.2003.10.008

Cited by 25 publications

(13 citation statements)

References 26 publications

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“…Our results were similar to previous studies with IFN-α treatment in various cell lines, including hematopoietic (H9) (21), Ba/F3 pro-B cells (22), and HCC (23); yet, discorded with some reports in chronic myelogenous leukemia (K562) (24), carcinoid tumor Bon1 (25), and human glioblastoma, U-373MG and T98G (26). Therefore, the influence of IFN-α on the cell cycle progression appears to be variable.…”

Section: Discussionsupporting

confidence: 91%

Fluoxetine regulates cell growth inhibition of interferon-α

Lin¹,

Chiu

et al. 2016

International Journal of Oncology

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Abstract. Fluoxetine, a well-known anti-depression agent, may act as a chemosensitizer to assist and promote cancer therapy. However, how fluoxetine regulates cellular signaling to enhance cellular responses against tumor cell growth remains unclear. In the present study, addition of fluoxetine promoted growth inhibition of interferon-alpha (IFN-α) in human bladder carcinoma cells but not in normal uroepithelial cells through lessening the IFN-α-induced apoptosis but switching to cause G1 arrest, and maintaining the IFN-α-mediated reduction in G2/M phase. Activations and signal transducer and transactivator (STAT)-1 and peroxisome proliferator-activated receptor alpha (PPAR-α) were involved in this process. Chemical inhibitions of STAT-1 or PPAR-α partially rescued bladder carcinoma cells from IFN-α-mediated growth inhibition via blockades of G1 arrest, cyclin D1 reduction, p53 downregulation and p27 upregulation in the presence of fluoxetine. However, the functions of both proteins were not involved in the control of fluoxetine over apoptosis and maintained the declined G2/M phase of IFN-α. These results indicated that activation of PPAR-α and STAT-1 participated, at least in part, in growth inhibition of IFN-α in the presence of fluoxetine.

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Section: Discussionsupporting

confidence: 91%

Fluoxetine regulates cell growth inhibition of interferon-α

Lin¹,

Chiu

et al. 2016

International Journal of Oncology

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“…In vitro, IFNa has been shown to inhibit proliferation of various cell lines by inducing cell accumulation in S-phase. [25][26][27] Our results concur with these observations as 4T1 cells were accumulating in S-phase, but not undergoing apoptosis after exposure to human hybrid interferon protein or rAd-IFNa2a1 (Figure 1). These results suggest that IFNa2a1 has a direct antiproliferative effect on the 4T1 cells but does not induce cell death in the absence of additional stimuli.…”

Section: Discussionsupporting

confidence: 88%

Adenovirus delivery provides extended interferon-α exposure and augments treatment of metastatic carcinoma

Brin¹,

Atencio²,

Helmich³

et al. 2006

Cancer Gene Ther

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Type I interferons (e.g. IFNa2b) have been successfully used to treat a variety of hematological malignancies, but have not been efficacious for treatment of most solid tumors. We tested the hypothesis that delivery of type I interferon utilizing recombinant adenovirus (rAd) vectors may improve treatment efficacy of metastatic carcinomas by providing increased interferon exposure resulting from continuous transgene expression. Treatment of mice with a rAd-vector expressing hybrid-IFN (rAd-IFNa2a1) inhibited 4T1 mammary carcinoma tumor growth and induced tumor regression in a dose-dependent manner. Moreover, rAd-IFNa2a1 treatment reduced hepatic and pulmonary metastatic burden. A comparison of local and systemic routes of administration demonstrated that intratumoral delivery of rAd-IFNa2a1 was sufficient for inhibition of tumor growth. Moreover, it reduced toxicity associated with high-dose systemic IFNa2a1 exposure. Interestingly, antitumor activity following intratumoral treatment was due, in part, to the immunostimulatory capacity of the rAd vector component. Furthermore, systemic administration of rAd-IFNa2a1 potentiated the immunotherapeutic effect induced by local intralesional delivery of empty-rAd vector. These results suggest continuous interferon-a exposure may provide improved antitumor responses for metastatic carcinomas. Additionally, immunostimulatory responses induced by rAd-IFNa2a1 may mitigate the immune-evasive tumor microenvironment.

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“…Furthermore, several reports [47, 48] have indicated that Daudi cells are highly susceptible to IFNα-induced apoptosis, which makes them a less favourable target to use when studying the effect of pDC on NK cells. K562 cells, on the other hand, are more resistant to IFN-α induced apoptosis [49]. The studies also differ in the type of stimulus used to mature the pDC.…”

Section: Discussionmentioning

confidence: 99%

Human NK Cell Up-regulation of CD69, HLA-DR, Interferon γ Secretion and Cytotoxic Activity by Plasmacytoid Dendritic Cells is Regulated through Overlapping but Different Pathways

Benlahrech

Donaghy

Rozis

et al. 2009

Sensors

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Human plasmacytoid dendritic cells secrete high levels of IFNα and are thus implicated in the activation of NK cells. Activated NK cells are characterised by the up-regulation of CD69 and MHC class II DR expression, secretion of IFN γ and enhanced cytotoxicity. We show that pDC mediate these processes by different mechanisms, some of which overlap. Human NK cells were analysed after co-culture with immature or CpG-matured blood pDC or with supernatant from these cells. Maximal CD69 expression by NK cells was mediated by supernatant from mature pDC and did not require pDC contact. Up-regulation was due in part to IFNα but also to factors in IFNα negative supernatant from immature DC. HLA-DR expression was independent of secreted molecules but required contact with immature or mature DC. Enhanced NK cytotoxicity, measured by killing of K562 targets and expression of CD107a, was mediated by multiple factors including type I IFN, supernatant from immature pDC cultures and contact with immature or mature pDC. These factors act cumulatively to enhance cytotoxcity. Thus different parameters of pDC mediated NK cell activation are regulated by distinct pathways.

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Interferon-alpha suppresses proliferation of chronic myelogenous leukemia cells K562 by extending cell cycle S-phase without inducing apoptosis

Cited by 25 publications

References 26 publications

Fluoxetine regulates cell growth inhibition of interferon-α

Fluoxetine regulates cell growth inhibition of interferon-α

Adenovirus delivery provides extended interferon-α exposure and augments treatment of metastatic carcinoma

Human NK Cell Up-regulation of CD69, HLA-DR, Interferon γ Secretion and Cytotoxic Activity by Plasmacytoid Dendritic Cells is Regulated through Overlapping but Different Pathways

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