Coordinated induction of cell survival signaling in the inflamed microenvironment of the prostate

McIlwain, David W.; Zoetemelk, Marloes; Myers, Jason D.; Edwards, Marshé T.; Snider, Brandy M.; Jerde, Travis J.

doi:10.1002/pros.23161

Cited by 9 publications

(5 citation statements)

References 34 publications

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“…As part of the CPC, survivin along with members Borealin, INCENP and Aurora B kinase orient the chromosomes during mitosis. Previously, our lab has demonstrated that survivin is juxtaposed to inflammation in human prostate cancer specimens and may play a role in repair and recovery of prostatic tissue [ 30 ]. Attempts at directly targeting survivin have ultimately failed in clinic, therefore new approaches or therapeutics that in some way block the expression or function of survivin are needed.…”

Section: Introductionmentioning

confidence: 99%

APE1/Ref-1 redox-specific inhibition decreases survivin protein levels and induces cell cycle arrest in prostate cancer cells

et al. 2017

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Section: Introductionmentioning

confidence: 99%

APE1/Ref-1 redox-specific inhibition decreases survivin protein levels and induces cell cycle arrest in prostate cancer cells

et al. 2017

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“…In this situation to increase the survival prospects of prostate epithelium against harmful factors, the synthesis of a variety of factors increases led by growth factors. Thus the hyperproliferative environment developing in prostate tissue forms an appropriate environment for cancer formation [15].…”

Section: Discussionmentioning

confidence: 99%

Comparison of serum acetyl hydrolase (PAF‐AH) and paraoxonase 1 (PON1) values between prostate cancer patients and a control group

Benli̇

Bayrak

Çırakoğlu

et al. 2017

The Kaohsiung J of Med Scie

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The aim of the study was to measure platelet-activating factor acetyl hydrolase (PAF-AH) and paraoxonase (PON1) enzyme activity levels in patients with high Psa values to compare with healthy peers and also to determine the efficacy of these parameters in predicting pathologic results of patients with high Psa values. This study included 66 patients with Psa value > 4 ng/dl (Group 1) and 44 patients with Psa <4 ng/dl (Group 2) for a total of 110 patients. Parameters measured in serum of PON1, PAF-AH, and MDA were compared between the groups. Additionally the same parameters were compared between patients with prostate biopsy performed due to high Psa and diagnosed with cancer and the control group with normal Psa values. The PAF-AH activity in Group 1 was 125.17 ± 8.64 and in Group 2 was 120.08 ± 9.23 U/ml (p = 0.003). The PON1 activity was 63.12 ± 6.74 and 65.91 ± 7.77 U/ml in the groups, respectively (p = 0.04). Additionally, there were significant differences identified between the control group and PCa diagnosis group in terms of PAF-AH and PON1 activities (p = 0.004 and p = 0.02, respectively). The enzyme activity of PAF-AH and PON1 measured in serum of patients with high Psa value and patients with diagnosis of prostate cancer (PCa) were identified to have changed by a significant amount compared to healthy peers with normal Psa value. It was concluded that these parameters may be beneficial markers for use in assessment of patients with high Psa value.

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“…Tissues were fixed at room temperature overnight in 10% neutral buffered formalin, and processed routinely through ethanol into xylene. Processed tissues were embedded in paraffin and cut on a microtome into 5-mm sections, mounted on positively charged slides, and baked at 60 C. Sections from the CisRef-TMA were stained with the APE1/Ref-1 antibody by the Indiana IF and IHC IF protocols were followed as described previously (31). Sections were processed routinely and subjected to heatinduced antigen retrieval in 10 mmol/L citrate buffer.…”

Section: Human Specimensmentioning

confidence: 99%

“…Sections were blocked at ambient temperature with a BSA-Donkey serum blocking medium for 2-4 hours, and incubated with the same blocking medium containing the indicated primary antibodies overnight at 4 C. Primary antibodies and dilutions included rabbit survivin (1:100, Cell Signaling Technology), mouse APE1/Ref-1 (1:200, Novus Biologicals), rabbit BrdU (1:200, Cell Signaling Technology), and mouse PanCK (1:200, Cell Signaling Technology). After incubation, all sections were washed with 1Â PBS-Tween and incubated with blocking medium containing with the species-specific (Invitrogen) IgG Alexa 488 and IgG Alexa 594-conjugated secondary antibody targeting rabbit or mouse for 1 hour at room tem-perature at a dilution of 1:200 as optimized previously (31). Nuclei were stained by incubation with Hoechst 33258 Nuclear Stain (Sigma) at a concentration of 1 mg/mL.…”

Section: Human Specimensmentioning

confidence: 99%

Antitumor Activity and Mechanistic Characterization of APE1/Ref-1 Inhibitors in Bladder Cancer

Fishel

Xia

McGeown

et al. 2019

Molecular Cancer Therapeutics

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Bladder cancer is the ninth most common cause of cancerrelated deaths worldwide. Although cisplatin is used routinely in treating bladder cancer, refractory disease remains lethal for many patients. The recent addition of immunotherapy has improved patient outcomes; however, a large cohort of patients does not respond to these treatments. Therefore, identification of innovative molecular targets for bladder cancer is crucial. Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) is a multifunctional protein involved in both DNA repair and activation of transcription factors through reduction-oxidation (redox) regulation. High APE1/ Ref-1 expression is associated with shorter patient survival time in many cancer types. In this study, we found high APE1/ Ref-1 expression in human bladder cancer tissue relative to benign urothelium. Inhibition of APE1/Ref-1 redox signaling using APE1/Ref-1-specific inhibitors attenuates bladder cancer cell proliferation in monolayer, in three-dimensional cultures, and in vivo. This inhibition corresponds with an increase in apoptosis and decreased transcriptional activity of NF-kB and STAT3, transcription factors known to be regulated by APE1/Ref-1, resulting in decreased expression of downstream effectors survivin and Cyclin D1 in vitro and in vivo. We also demonstrate that in vitro treatment of bladder cancer cells with APE1/Ref-1 redox inhibitors in combination with standard-of-care chemotherapy cisplatin is more effective than cisplatin alone at inhibiting cell proliferation. Collectively, our data demonstrate that APE1/Ref-1 is a viable drug target for the treatment of bladder cancer, provide a mechanism of APE1/Ref-1 action in bladder cancer cells, and support the use of novel redox-selective APE1/Ref-1 inhibitors in clinical studies.Significance: This work identifies a critical mechanism for APE1/Ref-1 in bladder cancer growth and provides compelling preclinical data using selective redox activity inhibitors of APE1/Ref-1 in vitro and in vivo.

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Coordinated induction of cell survival signaling in the inflamed microenvironment of the prostate

Cited by 9 publications

References 34 publications

APE1/Ref-1 redox-specific inhibition decreases survivin protein levels and induces cell cycle arrest in prostate cancer cells

APE1/Ref-1 redox-specific inhibition decreases survivin protein levels and induces cell cycle arrest in prostate cancer cells

Comparison of serum acetyl hydrolase (PAF‐AH) and paraoxonase 1 (PON1) values between prostate cancer patients and a control group

Antitumor Activity and Mechanistic Characterization of APE1/Ref-1 Inhibitors in Bladder Cancer

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