Proliferation Independent Activation of Programmed Cell Death as a Novel Therapy for Prostate Cancer

Furuya, Yuzo; Berges, Richard S.; Lundmo, Per I.; Isaacs, John T.

doi:10.1007/978-1-4757-9217-1_9

Cited by 31 publications

(37 citation statements)

References 49 publications

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“…Thapsigargin, an inhibitor of the Ca 2ϩ -ATPase of endoplasmic reticulum, has been shown to produce an increase in intracellular calcium levels in numerous cell types (32-34). Additionally, prolonged thapsigargin treatment has been shown to induce apoptotic cell death in various cell models (23)(24)(25). Our results clearly demonstrate that thapsigargin treatment significantly increased in situ transglutaminase activity in the cells transfected with tTG or Myr/Pal-tTG, but not in cells transfected with the C277S mutants when compared with cells transfected with vector only (Fig.…”

Section: Expression Of Ttg Constructs In Hek293 Cells-to Deter-supporting

confidence: 62%

“…To accomplish this goal, HEK293 cells were transiently transfected with wild-type tTG (tTG) or tTG without transamidating activity ([C277S]tTG) that were tagged with a nuclear localization sequence (NLS), or a signal sequence that directed proteins to the plasma membrane (Myr/Pal) or with tTG or [C277S]tTG that lacked any added cellular localization sequences and therefore are predominantly cytosolic (17). Apoptosis was subsequently induced by treatment with thapsigargin, an inhibitor of the Ca 2ϩ -ATPase of endoplasmic reticulum that has been shown to induce apoptosis in different cell models (23)(24)(25). After induction of cell death differential effects of the tTG constructs on the apoptotic process were observed: (i) wildtype tTG without any added cellular localization signals facilitated apoptosis, (ii) transamidating inactive tTG localized in the nucleus (NLS-C277S) ameliorated apoptosis, and (iii) localizing tTG to the membrane had no effect on apoptosis.…”

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confidence: 99%

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Intracellular Localization and Activity State of Tissue Transglutaminase Differentially Impacts Cell Death

Milaković

Tucholski

McCoy

et al. 2004

Journal of Biological Chemistry

115

141

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Tissue transglutaminase (tTG) is a unique member of the transglutaminase family as it is both a transamidating enzyme and a GTPase. In the cell tTG is mostly cytosolic, however it is also found in the nucleus and associated with the plasma membrane. tTG can be proapoptotic, however anti-apoptotic activities of the enzyme have also been reported. To determine how the intracellular localization and transamidating activity of tTG modulates its effects on apoptosis, HEK293 cells were transiently transfected with tTG or [C277S]tTG (which lacks transamidating activity) constructs that were targeted to different intracellular compartments. Apoptosis was induced by thapsigargin treatment, which results in increased intracellular calcium concentrations. Cytosolic tTG was pro-apoptotic, while nuclear localization of [C277S]tTG attenuated apoptosis. Membrane-targeted tTG had neither pro-nor anti-apoptotic functions. This finding indicates for the first time that intracellular localization is an important determinant of the effect of tTG on apoptosis. Previous studies have suggested that tTG may modulate retinoblastoma (Rb) protein, an important suppressor of apoptosis. tTG interacted with Rb and after induction of apoptosis, the interaction of nuclear-targeted [C277S]tTG with Rb was increased significantly concomitant with an attenuation of apoptosis. In contrast, the interaction of nucleartargeted tTG with Rb was significantly decreased and apoptosis was not attenuated. These data suggest that tTG protects cells against apoptosis in response to stimuli that do not result in increased transamidating activity by translocating to the nucleus, and that complexing with Rb may be an important aspect of the protective effects of tTG.

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Section: Expression Of Ttg Constructs In Hek293 Cells-to Deter-supporting

confidence: 62%

mentioning

confidence: 99%

Intracellular Localization and Activity State of Tissue Transglutaminase Differentially Impacts Cell Death

Milaković

Tucholski

McCoy

et al. 2004

Journal of Biological Chemistry

115

141

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“…Cell-cycle inhibitors mimic the effect of MV on lymphoproliferation and p24 antigen production Cell-cycle blocking agents were used to induce phase-specific inhibition of the cell cycle and simulate the effect of MV on lymphoproliferation and p24 antigen production. Thapsigargin induces a block in G 0 (Furuya et al, 1994), nbutyrate at G 1a (Darzynkiewicz et al, 1981;Korin & Zack, 1998) and hydroxyurea in G 1 /S (Maurer-Schultze et al, 1988). Thapsigargin failed to produce consistent dosedependent reductions in either lymphoproliferation or p24 antigen production (Fig.…”

Section: Blocks Hiv-1 Reverse Transcription In Hiv-1-infected Pbmcsmentioning

confidence: 86%

Measles virus inhibits human immunodeficiency virus type 1 reverse transcription and replication by blocking cell-cycle progression of CD4+ T lymphocytes

Garcia

Griffin

et al. 2008

Journal of General Virology

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Acute measles virus (MV) infection results in a decrease in plasma human immunodeficiency virus type 1 (HIV-1) RNA levels in co-infected children. An in vitro peripheral blood mononuclear cell (PBMC) culture system was used to assess the mechanisms by which MV blocks HIV-1 replication. MV inhibited proliferation of CD4 + T lymphocytes, the target cell for HIV-1 replication. In the presence of MV, cells did not progress to G 1b and S phases, steps critical for the completion of HIV-1 reverse transcription and productive replication. This block in cell-cycle progression was characterized by an increased proportion of CD4 + and HIV-1-infected cells retained in the parental generation in PBMCs co-cultured with MV and HIV-1, and decreased levels of cyclins and RNA synthesis. Early HIV-1 replication was also inhibited in the presence of MV, as measured by reduced expression of a luciferase reporter gene and lower levels of both early (LTR) and late (LTR-gag) DNA intermediates of HIV-1 reverse transcription in the presence of CCR5-tropic HIV-1. The effects of MV on lymphoproliferation and p24 antigen production were reproduced by n-butyrate and hydroxyurea, drugs that block the cell cycle in G 1a and G 1 /S, respectively. It was concluded that MV inhibits HIV-1 productive replication in part by blocking the proliferation of CD4 + T lymphocytes.

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“…192 There are at least three cell proliferation independent methods which can be used to increase the apoptotic rates of androgen-independent prostate cancer cells. 192 The ®rst approach is to use the host immune system to evoke, or enhance a cytotoxic anti-tumour response. Because both the growth and metastatic potential of a tumour are dependent on angiogenesis, the second approach is to block the host development of tumour blood supply.…”

Section: Medical Approaches In the Management Of Prostate Cancermentioning

confidence: 99%

Molecular and cellular biology of prostate cancer—the role of apoptosis as a target for therapy

Costa-Pereira

Cotter

1999

Prostate Cancer Prostatic Dis

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Despite the high incidence and mortality rate of prostate cancer, the molecular mechanisms underlying the progression of the disease remain to be fully elucidated. This paper reviews the current state of knowledge on prostatic carcinogenesis, focusing not only on the molecular genetics of prostate cancer, but also on the role of oncogenes, tumour suppressor genes, and growth factors. The remarkable ability of prostate cancer cells to survive androgen withdrawal and apoptosis are discussed, with particular emphasis on how apoptosis may be manipulated from a therapeutic viewpoint.

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Proliferation Independent Activation of Programmed Cell Death as a Novel Therapy for Prostate Cancer

Cited by 31 publications

References 49 publications

Intracellular Localization and Activity State of Tissue Transglutaminase Differentially Impacts Cell Death

Intracellular Localization and Activity State of Tissue Transglutaminase Differentially Impacts Cell Death

Measles virus inhibits human immunodeficiency virus type 1 reverse transcription and replication by blocking cell-cycle progression of CD4+ T lymphocytes

Molecular and cellular biology of prostate cancer—the role of apoptosis as a target for therapy

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