scholarly journals Heme Oxygenase-1 Inhibition Sensitizes Human Prostate Cancer Cells towards Glucose Deprivation and Metformin-Mediated Cell Death

2019 ◽  
Vol 20 (10) ◽  
pp. 2593 ◽  
Author(s):  
Marco Raffaele ◽  
Valeria Pittalà ◽  
Veronica Zingales ◽  
Ignazio Barbagallo ◽  
Loredana Salerno ◽  
...  

High levels of heme oxygenase (HO)-1 have been frequently reported in different human cancers, playing a major role in drug resistance and regulation of cancer cell redox homeostasis. Metformin (MET), a drug widely used for type 2 diabetes, has recently gained interest for treating several cancers. Recent studies indicated that the anti-proliferative effects of metformin in cancer cells are highly dependent on glucose concentration. The present work was directed to determine whether use of a specific inhibitor of HO-1 activity, alone or in combination with metformin, affected metastatic prostate cancer cell viability under different concentrations of glucose. MTT assay and the xCELLigence system were used to evaluate cell viability and cell proliferation in DU145 human prostate cancer cells. Cell apoptosis and reactive oxygen species were analyzed by flow cytometry. The activity of HO-1 was inhibited using a selective imidazole-based inhibitor; genes associated with antioxidant systems and cell death were evaluated by qRT-PCR. Our study demonstrates that metformin suppressed prostate cancer growth in vitro and increased oxidative stress. Disrupting the antioxidant HO-1 activity, especially under low glucose concentration, could be an attractive approach to potentiate metformin antineoplastic effects and could provide a biochemical basis for developing HO-1-targeting drugs against solid tumors.

2010 ◽  
Vol 9 (1) ◽  
pp. 182 ◽  
Author(s):  
Ricardo Parrondo ◽  
Alicia Pozas ◽  
Teresita Reiner ◽  
Priyamvada Rai ◽  
Carlos Perez-Stable

2018 ◽  
Vol 120 (4) ◽  
pp. 6264-6276 ◽  
Author(s):  
Benjamin M. Johnson ◽  
Faisal F. Y. Radwan ◽  
Azim Hossain ◽  
Bently P. Doonan ◽  
Jessica D. Hathaway‐Schrader ◽  
...  

1997 ◽  
Vol 148 (2) ◽  
pp. 105 ◽  
Author(s):  
Sanjeewani T. Palayoor ◽  
Edward A. Bump ◽  
Beverly A. Teicher ◽  
C. Norman Coleman

2015 ◽  
Vol 35 (5) ◽  
pp. 429-434 ◽  
Author(s):  
Hong-Tai Chang ◽  
Chiang-Ting Chou ◽  
Chia-Cheng Yu ◽  
Jeng-Yu Tsai ◽  
Te-Kung Sun ◽  
...  

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Bin Pan ◽  
Yunlin Ye ◽  
Haiping Liu ◽  
Jianli Zhen ◽  
Hongmei Zhou ◽  
...  

Upregulated gene 11 (URG11), a new gene upregulated by hepatitis B virus X protein, is involved in the development and progression of several tumors, including liver, stomach, lung, and colon cancers. However, the role of URG11 in prostate cancer remains yet to be elucidated. By determined expression in human prostate cancer tissues, URG11 was found significantly upregulated and positively correlated with the severity of prostate cancer, compared with that in benign prostatic hyperplasia tissues. Further, the mRNA and protein levels of URG11 were significantly upregulated in human prostate cancer cell lines (DU145, PC3, and LNCaP), compared with human prostate epithelial cell line (RWPE-1). Moreover, by the application of siRNA against URG11, the proliferation, migration, and invasion of prostate cancer cells were markedly inhibited. Genetic knockdown of URG11 also induced cell cycle arrest at G1/S phase, induced apoptosis, and decreased the expression level of β-catenin in prostate cancer cells. Overexpression of URG11 promoted the expression of β-catenin, the growth, the migration, and invasion ability of prostate cancer cells. Taken together, this study reveals that URG11 is critical for the proliferation, migration, and invasion in prostate cancer cells, providing the evidence of URG11 to be a novel potential therapeutic target of prostate cancer.


Toxicology ◽  
2015 ◽  
Vol 329 ◽  
pp. 88-97 ◽  
Author(s):  
Kotamballi N. Chidambara Murthy ◽  
Guddadarangavvanahally K. Jayaprakasha ◽  
Bhimanagouda S Patil

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1025-1025 ◽  
Author(s):  
Mikhail Kolonin ◽  
Anna Sergeeva ◽  
Daniela Staquicini ◽  
Jeffrey J. Molldrem ◽  
Renata Pasqualini ◽  
...  

Abstract Human prostate cancer non-randomly metastasizes to the bone marrow, but the biological basis for such site-specific tropism remains largely unresolved. Differential expression of molecules in the bone marrow microenvironment "niche" has recently been proposed to play a role. In previous work, combinatorial selection of random peptide libraries in end-of-life cancer patients has revealed an unexpected interaction between the receptor for advanced glycation end products (RAGE), a molecule expressed on malignant cell surfaces in advanced prostate cancer, and proteinase 3 (PR3), a serine protease abundantly present on neutrophils and promyelocytes within the bone marrow microenvironment. Because RAGE is selectively overexpressed in prostate cancer bone metastases, we hypothesize here that its specific binding to PR3 might mediate homing of prostate cancer cells to the bone marrow. We demonstrate that PR3 non-proteolytically binds to RAGE on prostate cancer cell surfaces and thereby promotes tumor cell activation and motility. We also show that the downstream signal transduction cascade triggered by RAGE/PR3 binding involves p44/42 (Erk1/2) and JNK1 phosphorylation. Finally, we use a mouse model of experimental metastasis to demonstrate that RAGE protein expression on human prostate cancer cells promotes their homing to bone marrow within a short time frame. These results validate a functional protein interaction between RAGE and PR3 and uncover a mechanism through which neutrophils mediate prostate cancer cell metastasis to the skeleton. Disclosures Sergeeva: Astellas: Patents & Royalties. Molldrem:Astellas Pharma: Patents & Royalties.


Life Sciences ◽  
2009 ◽  
Vol 85 (11-12) ◽  
pp. 421-430 ◽  
Author(s):  
V. Alonso ◽  
F.C. Pérez-Martínez ◽  
F.J. Calahorra ◽  
P. Esbrit

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