Metabolic Stress Induced by Arginine Deprivation Induces Autophagy Cell Death in Prostate Cancer

Background: Prostate cancer is the second most common cancer in American men. The development of alternative preventative and/or treatment options utilizing a combination of phytochemicals and chemotherapeutic drugs could be an attractive alternative compared to conventional carcinoma treatments. Genistein isoflavone is the primary dietary phytochemical found in soy and has demonstrated anti-tumor activities in LNCaP prostate cancer cells. Topotecan Hydrochloride (Hycamtin) is an FDA-approved chemotherapy for secondary treatment of lung, ovarian and cervical cancers. The purpose of this study was to detail the potential activation of the intrinsic apoptotic pathway in LNCaP prostate cancer cells through genistein-topotecan combination treatments. Methods: LNCaP cells were cultured in complete RPMI medium in a monolayer (70-80% confluency) at 37ºC and 5% CO2. Treatment consisted of single and combination groups of genistein and topotecan for 24 hours. The treated cells were assayed for i) growth inhibition through trypan blue exclusion assay and microphotography, ii) classification of cellular death through acridine/ ethidium bromide fluorescent staining, and iii) activation of the intrinsic apoptotic pathway through Jc-1: mitochondrial membrane potential assay, cytochrome c release and Bcl-2 protein expression.Results: The overall data indicated that genistein-topotecan combination was significantly more efficacious in reducing the prostate carcinoma’s viability compared to the single treatment options. In all treatment groups, cell death occurred primarily through the activation of the intrinsic apoptotic pathway.Conclusion: The combination of topotecan and genistein has the potential to lead to treatment options with equal therapeutic efficiency as traditional chemo- and radiation therapies, but lower cell cytotoxicity and fewer side effects in patients. Key words: topotecan; genistein; intrinsic apoptotic cell death

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Killing Prostate Cancer Cells and Endothelial Cells with a VEGF-Triggered Cell Death Receptor

10.21236/ada476353 ◽

2005 ◽

Author(s):

Timothy P. Quinn

Keyword(s):

Prostate Cancer ◽

Endothelial Cells ◽

Cell Death ◽

Cancer Cells ◽

Death Receptor ◽

Prostate Cancer Cells ◽

Cell Death Receptor

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Molecular Basis of Autophagic Cell Death in Prostate Cancer

10.21236/ada506319 ◽

2009 ◽

Author(s):

Ramesh Kaini

Keyword(s):

Prostate Cancer ◽

Cell Death ◽

Molecular Basis ◽

Autophagic Cell Death

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Elevated Expression of Glycerol-3-Phosphate Phosphatase as a Biomarker of Poor Prognosis and Aggressive Prostate Cancer

Cancers ◽

10.3390/cancers13061273 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1273

Author(s):

Mohamed Amine Lounis ◽

Veronique Ouellet ◽

Benjamin Péant ◽

Christine Caron ◽

Zhenhong Li ◽

...

Keyword(s):

Prostate Cancer ◽

Bone Metastasis ◽

Biochemical Recurrence ◽

Poor Prognosis ◽

Cox Regression ◽

Specific Antigen ◽

Metabolic Stress ◽

Cancer Specific Survival ◽

High Risk Prostate Cancer ◽

Increased Risk

The limitations of the biomarker prostate-specific antigen (PSA) necessitate the pursuit of biomarkers capable of better identifying high-risk prostate cancer (PC) patients in order to improve their therapeutic management and outcomes. Aggressive prostate tumors characteristically exhibit high rates of glycolysis and lipogenesis. Glycerol 3-phosphate phosphatase (G3PP), also known as phosphoglycolate phosphatase (PGP), is a recently identified mammalian enzyme, shown to play a role in the regulation of glucose metabolism, lipogenesis, lipolysis, and cellular nutrient-excess detoxification. We hypothesized that G3PP may relieve metabolic stress in cancer cells and assessed the association of its expression with PC patient prognosis. Using immunohistochemical staining, we assessed the epithelial expression of G3PP in two different radical prostatectomy (RP) cohorts with a total of 1797 patients, for whom information on biochemical recurrence (BCR), metastasis, and mortality was available. The association between biomarker expression, biochemical recurrence (BCR), bone metastasis, and prostate cancer-specific survival was established using log-rank and multivariable Cox regression analyses. High expression of G3PP in PC epithelial cells is associated with an increased risk of BCR, bone metastasis, and PC-specific mortality. Multivariate analysis revealed high G3PP expression in tumors as an independent predictor of BCR and bone metastasis development. High G3PP expression in tumors from patients eligible for prostatectomies is a new and independent prognostic biomarker of poor prognosis and aggressive PC for recurrence, bone metastasis, and mortality.

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Poly (ADP-Ribose) Polymerase 1 Protein Expression in Normal Pancreas and Pancreatic Adenocarcinoma

Case Reports in Gastrointestinal Medicine ◽

10.1155/2020/2717150 ◽

2020 ◽

Vol 2020 ◽

pp. 1-4

Author(s):

Roberto Castiglione ◽

Aldo E. Calogero ◽

Enzo Vicari ◽

Giovanna Calabrini ◽

Anna Cosentino ◽

...

Keyword(s):

Prostate Cancer ◽

Pancreatic Cancer ◽

Cell Death ◽

Pancreatic Adenocarcinoma ◽

Cancer Tissue ◽

Normal Pancreas ◽

Normal Prostate ◽

Cytoplasmic Staining ◽

Cancer Of The Pancreas ◽

Parp 1

Pancreatic cancer is a most frequent cancer in Europe, and the majority of cases of cancer of the pancreas are diagnosed above the age of 65. Radical surgery is the first curative treatment of pancreatic cancer, and alternative or combined therapeutic options, in particular, consist of adjuvant or neoadjuvant chemotherapy, with or without radiotherapy. Many factors, including diet and genetics, have been implicated in the development of cancer of the pancreas. Poly (ADP-ribose) polymerase 1 (PARP-1) protein is required for translocation of the apoptosis-inducing factor (AIF) from the mitochondria to the nucleus. It is involved in programmed cell death processes. Different PARP-1 gene expression proteins have been observed in various tumors such as lung, ovarian, endometrial, skin, and glioblastoma. We evaluated the expression of PARP-1 protein in pancreatic adenocarcinoma and normal pancreas tissues by immunohistochemistry. Protein PARP-1 in the nucleus was found in all samples (normal pancreas and pancreatic adenocarcinoma tissues). No cytoplasmic staining was observed in any sample. PARP-1-positive cells resulted higher in the normal pancreas compared with the pancreas with adenocarcinoma. PARP-1 overexpression in prostate cancer tissue compared with normal prostate suggests a greater activity of PARP-1 in these tumors. These findings suggest that PARP-1 expression in prostate cancer is an attempt to trigger apoptosis in this type of tumor, similarl to that reported in other cancers. This finding suggests that PARP-1-mediated cell death pathways are inhibited in this cancer.

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