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Protective Effects of Caffeic Acid Phenethyl Ester (CAPE) and Novel Cape Analogue as Inducers of Heme Oxygenase-1 in Streptozotocin-Induced Type 1 Diabetic Rats
Open AccessCommunication

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

1
Department of Drug Science, Biochemistry Section, University of Catania, 95125 Catania, Italy
2
Department of Drug Science, Pharmaceutical Chemistry Section, University of Catania, 95125 Catania, Italy
3
Department of Biomedical and Biotechnological Sciences, University of Catania, 95125 Catania, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(10), 2593; https://doi.org/10.3390/ijms20102593
Received: 18 April 2019 / Revised: 16 May 2019 / Accepted: 23 May 2019 / Published: 27 May 2019
(This article belongs to the Special Issue Protective and Detrimental Role of Heme Oxygenase-1)
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. View Full-Text
Keywords: prostate cancer; heme oxygenase; metformin; apoptosis; ER stress; HO-1 activity inhibitor prostate cancer; heme oxygenase; metformin; apoptosis; ER stress; HO-1 activity inhibitor
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Raffaele, M.; Pittalà, V.; Zingales, V.; Barbagallo, I.; Salerno, L.; Li Volti, G.; Romeo, G.; Carota, G.; Sorrenti, V.; Vanella, L. Heme Oxygenase-1 Inhibition Sensitizes Human Prostate Cancer Cells towards Glucose Deprivation and Metformin-Mediated Cell Death. Int. J. Mol. Sci. 2019, 20, 2593.

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