scholarly journals HO-1 Modulates Aerobic Glycolysis through LDH in Prostate Cancer Cells

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 966
Author(s):  
Florencia Cascardo ◽  
Nicolás Anselmino ◽  
Alejandra Páez ◽  
Estefanía Labanca ◽  
Pablo Sanchis ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Aerobic Glycolysis ◽  
Heme Oxygenase 1 ◽  
Free Survival ◽  
Atp Production ◽  
Inflammatory Damage ◽  
Extracellular Lactate ◽  
Cellular Energetics ◽  
Lactate Levels

Prostate cancer (PCa) is the second most diagnosed malignancy and the fifth leading cause of cancer associated death in men worldwide. Dysregulation of cellular energetics has become a hallmark of cancer, evidenced by numerous connections between signaling pathways that include oncoproteins and key metabolic enzymes. We previously showed that heme oxygenase 1 (HO-1), a cellular homeostatic regulator counteracting oxidative and inflammatory damage, exhibits anti-tumoral activity in PCa cells, inhibiting cell proliferation, migration, tumor growth and angiogenesis. The aim of this study was to assess the role of HO-1 on the metabolic signature of PCa. After HO-1 pharmacological induction with hemin, PC3 and C4-2B cells exhibited a significantly impaired cellular metabolic rate, reflected by glucose uptake, ATP production, lactate dehydrogenase (LDH) activity and extracellular lactate levels. Further, we undertook a bioinformatics approach to assess the clinical significance of LDHA, LDHB and HMOX1 in PCa, identifying that high LDHA or low LDHB expression was associated with reduced relapse free survival (RFS). Interestingly, the shortest RFS was observed for PCa patients with low HMOX1 and high LDHA, while an improved prognosis was observed for those with high HMOX1 and LDHB. Thus, HO-1 induction causes a shift in the cellular metabolic profile of PCa, leading to a less aggressive phenotype of the disease.

Lamin B1 promotes tumor progression and metastasis in primary prostate cancer patients

2020 ◽  
Author(s):  
Fei Luo ◽  
Jiaxi Han ◽  
Yatong Chen ◽  
Kuo Yang ◽  
Zhihua Zhang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Progression ◽  
Cancer Metastasis ◽  
Disease Free Survival ◽  
Free Survival ◽  
Lamin B1 ◽  
Kaplan Meier ◽  
Primary Prostate Cancer ◽  
Clinical Relationship

Aims: To determine the role of lamin B1 (LMNB1) in the progression and metastasis of primary prostate cancer (PC). Patients & methods: Two PC cohorts were used to investigate the clinical relationship between LMNB1 expression and tumor progression and metastasis. Results: The qRT-PCR results revealed that LMNB1 expression was markedly increased in patients with aggressive features and was associated with worse prognosis. Logistic regression analyses indicated that LMNB1 expression is an independent risk factor for distant metastasis. Kaplan–Meier analysis showed that increased LMNB1 levels were related to poor disease-free survival in the primary PC cohort. Conclusion: This study reveals that upregulation of LMNB1 is associated with cancer metastasis and poor survival outcomes in primary PC patients.

Critical Role of Endogenous Heme Oxygenase 1 as a Tuner of the Invasive Potential of Prostate Cancer Cells

2009 ◽  
Vol 7 (11) ◽  
pp. 1745-1755 ◽  
Author(s):  
Geraldine Gueron ◽  
Adriana De Siervi ◽  
Mercedes Ferrando ◽  
Marcelo Salierno ◽  
Paola De Luca ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Heme Oxygenase ◽  
Critical Role ◽  
Heme Oxygenase 1 ◽  
Prostate Cancer Cells ◽  
Invasive Potential

scholarly journals Brain Glucose Metabolism: Integration of Energetics with Function

2019 ◽  
Vol 99 (1) ◽  
pp. 949-1045 ◽  
Author(s):  
Gerald A. Dienel
Keyword(s):  
Aerobic Glycolysis ◽  
Local Level ◽  
Nutritional Therapy ◽  
Brain Regions ◽  
Pentose Phosphate ◽  
Atp Production ◽  
Cellular Energetics ◽  
Excitatory Neurotransmission ◽  
Evaluation Of Data ◽  
Glycogen Turnover

Glucose is the long-established, obligatory fuel for brain that fulfills many critical functions, including ATP production, oxidative stress management, and synthesis of neurotransmitters, neuromodulators, and structural components. Neuronal glucose oxidation exceeds that in astrocytes, but both rates increase in direct proportion to excitatory neurotransmission; signaling and metabolism are closely coupled at the local level. Exact details of neuron–astrocyte glutamate–glutamine cycling remain to be established, and the specific roles of glucose and lactate in the cellular energetics of these processes are debated. Glycolysis is preferentially upregulated during brain activation even though oxygen availability is sufficient (aerobic glycolysis). Three major pathways, glycolysis, pentose phosphate shunt, and glycogen turnover, contribute to utilization of glucose in excess of oxygen, and adrenergic regulation of aerobic glycolysis draws attention to astrocytic metabolism, particularly glycogen turnover, which has a high impact on the oxygen–carbohydrate mismatch. Aerobic glycolysis is proposed to be predominant in young children and specific brain regions, but re-evaluation of data is necessary. Shuttling of glucose- and glycogen-derived lactate from astrocytes to neurons during activation, neurotransmission, and memory consolidation are controversial topics for which alternative mechanisms are proposed. Nutritional therapy and vagus nerve stimulation are translational bridges from metabolism to clinical treatment of diverse brain disorders.

Mechanistic association of Notch 3 protein with the chemotherapy response of localized prostate cancer

2017 ◽  
Vol 5 (2) ◽  
pp. 161-175
Author(s):  
ones Lorenzoni ◽  
Lutz Hartsell
Keyword(s):  
Prostate Cancer ◽  
Notch Signaling Pathway ◽  
Localized Prostate Cancer ◽  
Chemotherapy Response ◽  
Cancer Specific Survival ◽  
Free Survival ◽  
Notch 3 ◽  
Kaplan Meier

Prostate cancer is one of the most common cancers in American men. Genetics and age play a role in its development. Notch signaling pathway proteins are known to play critical roles in maintaining the balance between cell proliferation, differentiation and apoptosis, and thus it has been suggested that Notch may be responsible for the development and progression of human malignancies. The aim of this study is investigated the mechanistic role of Notch 3 with the chemotherapy response of patients with localized prostate cancer (PCa). A total of 772 patients with clinically localized PCa, confirmed by biopsy. Biochemical recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) were assessed with Kaplan-Meier curves. Various histopathological parameters were analyzed by univariate and multivariate analysis. Our results demonstrate that a high Notch 3 expression in prostate tumor represented a significantly higher possibility of being resistant to chemotherapy and reduced OS. Also, patients with high Notch 3 expression had a poorer prognosis than those with low Notch 3 expression. Further, in vitro studies showed that Notch 3 inhibition the proliferation, migration of invasiveness of prostate cancer. Consequently, we propose that Notch 3 protein is an important event that enhances tumor angiogenesis in human prostate cancer cells.

scholarly journals Nanocatalytic activity of clean-surfaced, faceted nanocrystalline gold enhances remyelination in animal models of multiple sclerosis

2019 ◽  
Author(s):  
Andrew P. Robinson ◽  
Joanne Zhongyan Zhang ◽  
Haley E. Titus ◽  
Molly Karl ◽  
Mikhail Merzliakov ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Animal Models ◽  
Oral Delivery ◽  
Aerobic Glycolysis ◽  
Differentiation Markers ◽  
Gold Nanocrystals ◽  
Extracellular Lactate ◽  
Lactate Levels ◽  
Key Indicators

AbstractDevelopment of pharmacotherapies that promote remyelination are a high priority for multiple sclerosis (MS) due to their potential for neuroprotection and restoration of function through repair of demyelinated lesions. A novel preparation of clean-surfaced, faceted gold nanocrystals demonstrated robust remyelinating activity in response to demyelinating agents in both chronic cuprizone and acute lysolecithin rodent animal models. Furthermore, oral delivery of gold nanocrystals improved motor functions of cuprizone-treated mice in both open field and kinematic gait studies. Gold nanocrystal treatment of oligodendrocyte precursor cells in culture resulted in oligodendrocyte maturation and expression of key myelin differentiation markers. Additional in vitro data demonstrated that these gold nanocrystals act via a novel energy metabolism pathway involving the enhancement of key indicators of aerobic glycolysis. In response to gold nanocrystals, co-cultured central nervous system cells exhibited elevated levels of the redox coenzyme nicotine adenine dinucleotide (NAD+), elevated total ATP levels, elevated extracellular lactate levels, and upregulation of myelin-synthesis related genes, collectively resulting in functional myelin generation. Based on these preclinical studies, clean-surfaced, faceted gold nanocrystals represent a novel remyelinating therapeutic for multiple sclerosis.One Sentence SummaryNanocatalytic activity of clean-surfaced, faceted gold nanocrystals results in robust remyelinating activity in demyelination animal models of multiple sclerosis.

888 THE ROLE OF HEME OXYGENASE-1 AND CARBON MONOXIDE (CO) IN REGULATION OF CHEMOTHERAPEUTIC RESPONSES IN PROSTATE CANCER

2009 ◽  
Vol 8 (4) ◽  
pp. 342
Author(s):  
B. Wegiel ◽  
A. Sachs ◽  
J. Persson ◽  
A. Bjartell ◽  
L.E. Otterbein
Keyword(s):  
Prostate Cancer ◽  
Carbon Monoxide ◽  
Heme Oxygenase ◽  
Heme Oxygenase 1

scholarly journals Consecutive Prostate Cancer Specimens Revealed Increased Aldo–Keto Reductase Family 1 Member C3 Expression with Progression to Castration-Resistant Prostate Cancer

2019 ◽  
Vol 8 (5) ◽  
pp. 601 ◽  
Author(s):  
Yu Miyazaki ◽  
Yuki Teramoto ◽  
Shinsuke Shibuya ◽  
Takayuki Goto ◽  
Kosuke Okasho ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Immunohistochemical Expression ◽  
Free Survival ◽  
Castration Resistant ◽  
Psa Progression ◽  
Prostatic Epithelium

Aldo-keto reductase family 1 member C3 (AKR1C3) is an enzyme in the steroidogenesis pathway, especially in formation of testosterone and dihydrotestosterone, and is believed to have a key role in promoting prostate cancer (PCa) progression, particularly in castration-resistant prostate cancer (CRPC). This study aims to compare the expression level of AKR1C3 between benign prostatic epithelium and cancer cells, and among hormone-naïve prostate cancer (HNPC) and CRPC from the same patients, to understand the role of AKR1C3 in PCa progression. Correlation of AKR1C3 immunohistochemical expression between benign and cancerous epithelia in 134 patient specimens was analyzed. Additionally, correlation between AKR1C3 expression and prostate-specific antigen (PSA) progression-free survival (PFS) after radical prostatectomy was analyzed. Furthermore, we evaluated the consecutive prostate samples derived from 11 patients both in the hormone-naïve and castration-resistant states. AKR1C3 immunostaining of cancer epithelium was significantly stronger than that of the benign epithelia in patients with localized HNPC (p < 0.0001). High AKR1C3 expression was an independent factor of poor PSA PFS (p = 0.032). Moreover, AKR1C3 immunostaining was significantly stronger in CRPC tissues than in HNPC tissues in the same patients (p = 0.0234). Our findings demonstrate that AKR1C3 is crucial in PCa progression.

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