Abstract B95: Targeting cancer cell metabolism: The combination of metformin and 2‐deoxyglucose induces p53 dependent apoptosis in prostate cancer cells

: Metabolic changes driven by the hostile tumor microenvironment surrounding cancer cells and effect of these changes on tumorigenesis and metastatic potential have been known for a long time. The usual point of interest is glucose and changes in its utilization by cancer cells, mainly in the form of the Warburg effect. However, amino acids, both intra- and extracellular, also represent an important aspect of tumour microenvironment, which can have a significant effect on cancer cell metabolism and overall development of the tumor. Namely alterations in metabolism of amino acids glutamine, sarcosine, aspartate, methionine and cysteine have been previously connected to the tumor progression and aggressivity of prostate cancer. The aim of this review is to pinpoint current gaps in our knowledge of the role of amino acids as a part of the tumor microenvironment and to show effect of various amino acids on cancer cell metabolism and metastatic potential. This review shows limitations and exceptions from the traditionally accepted model of Warburg effect in some cancer tissues, with the emphasis on prostate cancer, because the traditional definition of Warburg effect as a metabolic switch to aerobic glycolysis does not always apply. Prostatic tissue both in healthy and transformed state significantly differs in many metabolic aspects, including the metabolisms of glucose and amino acids, from metabolism of other tissues. Findings from different tissues are therefore not always interchangeable and have to be taken into account during experimentation modifying the environment of tumor tissue by amino acid supplementation or depletion, which could potentially serve as a new therapeutic approach.

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Inhibition of glypican-1 expression induces an activated fibroblast phenotype in a human bone marrow-derived stromal cell-line

Scientific Reports ◽

10.1038/s41598-021-88519-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Sukhneeraj P. Kaur ◽

Arti Verma ◽

Hee. K. Lee ◽

Lillie M. Barnett ◽

Payaningal R. Somanath ◽

...

Keyword(s):

Prostate Cancer ◽

Bone Marrow ◽

Cancer Cells ◽

Cancer Cell ◽

Stromal Cell ◽

Prostate Cancer Cell ◽

Bone Cells ◽

Human Bone ◽

Human Bone Marrow ◽

Prostate Cancer Cells

AbstractCancer-associated fibroblasts (CAFs) are the most abundant stromal cell type in the tumor microenvironment. CAFs orchestrate tumor-stromal interactions, and contribute to cancer cell growth, metastasis, extracellular matrix (ECM) remodeling, angiogenesis, immunomodulation, and chemoresistance. However, CAFs have not been successfully targeted for the treatment of cancer. The current study elucidates the significance of glypican-1 (GPC-1), a heparan sulfate proteoglycan, in regulating the activation of human bone marrow-derived stromal cells (BSCs) of fibroblast lineage (HS-5). GPC-1 inhibition changed HS-5 cellular and nuclear morphology, and increased cell migration and contractility. GPC-1 inhibition also increased pro-inflammatory signaling and CAF marker expression. GPC-1 induced an activated fibroblast phenotype when HS-5 cells were exposed to prostate cancer cell conditioned media (CCM). Further, treatment of human bone-derived prostate cancer cells (PC-3) with CCM from HS-5 cells exhibiting GPC-1 loss increased prostate cancer cell aggressiveness. Finally, GPC-1 was expressed in mouse tibia bone cells and present during bone loss induced by mouse prostate cancer cells in a murine prostate cancer bone model. These data demonstrate that GPC-1 partially regulates the intrinsic and extrinsic phenotype of human BSCs and transformation into activated fibroblasts, identify novel functions of GPC-1, and suggest that GPC-1 expression in BSCs exerts inhibitory paracrine effects on the prostate cancer cells. This supports the hypothesis that GPC-1 may be a novel pharmacological target for developing anti-CAF therapeutics to control cancer.

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Distinct roles for the RNA-binding protein Staufen1 in prostate cancer

BMC Cancer ◽

10.1186/s12885-021-07844-2 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Kristen A. Marcellus ◽

Tara E. Crawford Parks ◽

Shekoufeh Almasi ◽

Bernard J. Jasmin

Keyword(s):

Prostate Cancer ◽

Cancer Cells ◽

Cancer Cell ◽

Rna Binding ◽

Prostate Cancer Cell ◽

Rna Binding Protein ◽

Migration And Invasion ◽

Human Prostate Cancer ◽

Prostate Cancer Cells ◽

Prostate Cells

Abstract Background Prostate cancer is one of the most common malignant cancers with the second highest global rate of mortality in men. During the early stages of disease progression, tumour growth is local and androgen-dependent. Despite treatment, a large percentage of patients develop androgen-independent prostate cancer, which often results in metastases, a leading cause of mortality in these patients. Our previous work on the RNA-binding protein Staufen1 demonstrated its novel role in cancer biology, and in particular rhabdomyosarcoma tumorigenesis. To build upon this work, we have focused on the role of Staufen1 in other forms of cancer and describe here the novel and differential roles of Staufen1 in prostate cancer. Methods Using a cell-based approach, three independent prostate cancer cell lines with different characteristics were used to evaluate the expression of Staufen1 in human prostate cancer relative to control prostate cells. The functional impact of Staufen1 on several key oncogenic features of prostate cancer cells including proliferation, apoptosis, migration and invasion were systematically investigated. Results We show that Staufen1 levels are increased in all human prostate cancer cells examined in comparison to normal prostate epithelial cells. Furthermore, Staufen1 differentially regulates growth, migration, and invasion in the various prostate cancer cells assessed. In LNCaP prostate cancer cells, Staufen1 regulates cell proliferation through mTOR activation. Conversely, Staufen1 regulates migration and invasion of the highly invasive, bone metastatic-derived, PC3 prostate cells via the activation of focal adhesion kinase. Conclusions Collectively, these results show that Staufen1 has a direct impact in prostate cancer development and further demonstrate that its functions vary amongst the prostate cancer cell types. Accordingly, Staufen1 represents a novel target for the development of much-needed therapeutic strategies for prostate cancer.

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Apoptosis triggered by isoquercitrin in bladder cancer cells by activating the AMPK-activated protein kinase pathway

Food & Function ◽

10.1039/c7fo00778g ◽

2017 ◽

Vol 8 (10) ◽

pp. 3707-3722 ◽

Cited By ~ 20

Author(s):

Ping Wu ◽

Siyuan Liu ◽

Jianyu Su ◽

Jianping Chen ◽

Lin Li ◽

...

Keyword(s):

Bladder Cancer ◽

Protein Kinase ◽

Cancer Cells ◽

Cancer Cell ◽

Cell Metabolism ◽

Bladder Cancer Cell ◽

Bladder Cancer Cells ◽

Immunoblotting Assay ◽

Cancer Cell Metabolism ◽

Kinase Pathway

Our findings provide comprehensive evidence that isoquercitrin (ISO) influenced T24 bladder cancer cell metabolism by activating the AMPK pathway as identified by combination with metabolomics and immunoblotting assay.

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How can food extracts consumed in the Mediterranean and East Asia suppress prostate cancer proliferation?

British Journal Of Nutrition ◽

10.1017/s0007114511005770 ◽

2011 ◽

Vol 108 (3) ◽

pp. 424-430 ◽

Cited By ~ 4

Author(s):

Mu Yao ◽

Chanlu Xie ◽

Maryrose Constantine ◽

Sheng Hua ◽

Brett D. Hambly ◽

...

Keyword(s):

Prostate Cancer ◽

Cell Proliferation ◽

East Asia ◽

Cancer Cells ◽

Cancer Cell ◽

Cancer Progression ◽

Prostate Cancer Cell ◽

Cancer Cell Proliferation ◽

Prostate Cancer Cells ◽

The Mediterranean

We have developed a blend of food extracts commonly consumed in the Mediterranean and East Asia, named blueberry punch (BBP), with the ultimate aim to formulate a chemoprevention strategy to inhibit prostate cancer progression in men on active surveillance protocol. We demonstrated previously that BBP inhibited prostate cancer cell proliferation in vitro and in vivo. The purpose of this study was to determine the molecular mechanism responsible for the suppression of prostate cancer cell proliferation by BBP. Treatment of lymph node-metastasised prostate cancer cells (LNCaP) and bone-metastasised prostate cancer cells (PC-3 and MDA-PCa-2b) with BBP (up to 0·8 %) for 72 h increased the percentage of cells at the G0/G1 phase and decreased those at the S and G2/M phases. The finding was supported by the reduction in the percentage of Ki-67-positive cells and of DNA synthesis measured by the incorporation of 5-ethynyl-2′-deoxyuridine. Concomitantly, BBP treatment decreased the protein levels of phosphorylated retinoblastoma, cyclin D1 and E, cyclin-dependent kinase (CDK) 4 and 2, and pre-replication complex (CDC6 and MCM7) in LNCaP and PC-3 cells, whereas CDK inhibitor p27 was elevated in these cell lines. In conclusion, BBP exerts its anti-proliferative effect on prostate cancer cells by modulating the expression and phosphorylation of multiple regulatory proteins essential for cell proliferation.

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Targeting cancer cell metabolism with mitochondria-immobilized phosphorescent cyclometalated iridium(iii) complexes

Chemical Science ◽

10.1039/c6sc02901a ◽

2017 ◽

Vol 8 (1) ◽

pp. 631-640 ◽

Cited By ~ 93

Author(s):

Jian-Jun Cao ◽

Cai-Ping Tan ◽

Mu-He Chen ◽

Na Wu ◽

De-Yang Yao ◽

...

Keyword(s):

Cancer Cells ◽

Cancer Cell ◽

Rational Design ◽

Cell Metabolism ◽

Mitochondrial Metabolism ◽

Cancer Cell Metabolism

We report a rational design and mechanism studies of mitochondria-immobilized iridium(iii) complexes that can kill cancer cells by targeting mitochondrial metabolism.

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Roles of microRNA in prostate cancer cell metabolism

The International Journal of Biochemistry & Cell Biology ◽

10.1016/j.biocel.2018.07.003 ◽

2018 ◽

Vol 102 ◽

pp. 109-116 ◽

Cited By ~ 3

Author(s):

Khanmi Kasomva ◽

Arnab Sen ◽

Michael Gabriel Paulraj ◽

Stephen Sailo ◽

Vandana Raphael ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Cell ◽

Prostate Cancer Cell ◽

Cell Metabolism ◽

Cancer Cell Metabolism

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Abstract 2450: CaMKK2-AMPK signaling facilitates androgen-mediated prostate cancer cell metabolism

10.1158/1538-7445.am2014-2450 ◽

2014 ◽

Cited By ~ 1

Author(s):

Daniel E. Frigo ◽

Yan Shi ◽

Jenny J. Han ◽

Efrosini Tsouko ◽

Michael M. Ittmann

Keyword(s):

Prostate Cancer ◽

Cancer Cell ◽

Prostate Cancer Cell ◽

Cell Metabolism ◽

Ampk Signaling ◽

Cancer Cell Metabolism

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Cisplatin and Paclitaxel Modulated the Cell Survival Potential of Prostate Cancer Cells

Proceedings ◽

10.3390/proceedings2019040042 ◽

2020 ◽

Vol 40 (1) ◽

pp. 42

Author(s):

Kashani ◽

Kilbas ◽

Yerlikaya ◽

Gurkan ◽

Arisan

Keyword(s):

Prostate Cancer ◽

Cell Viability ◽

Cell Survival ◽

Cancer Cells ◽

Cancer Cell ◽

Prostate Cancer Cell ◽

Dependent Manner ◽

Prostate Cancer Cells ◽

Cell Viability Assay ◽

Chemotherapy Drugs

Prostate cancer is the second common cause of death among men worldwide. In the treatment of prostate cancer, conventional chemotherapeutics are commonly used. The plant alkaloid Paclitaxel and platinum-based cisplatin are the most common chemotherapy drugs. The transcription factor p53 has a potential target in the regulation of cell response to DNA damage of prostate cancer. Although the effectiveness of these drugs on prostate cancer cell progression had been proved, the mechanistic action of these drugs on the progression of the disease is not detailed explained. In this study, we aim to examine the function of p53 overexpression in prostate cancer cell survival. Therefore, we treated wild type (wt) and p53 overexpressed PC3 (p53+) prostate cancer cells with cisplatin or paclitaxel. According to the MTT Cell Viability assay, cisplatin (12.5–25–50 µM) was found to be more effective decreasing PC3 and PC3 p53+ cell viability in a dose-dependent manner compared to paclitaxel (12.5–25–50 nM). Colony formation assay showed that treatment of cells with cisplatin or paclitaxel caused the loss of colony forming ability of PC3 and PC3 p53+ cells. In addition, the critical apoptotic markers Caspase-3 and Caspase-9 expressions were altered with cisplatin or paclitaxel treated PC3 wt and p53+ cells.

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