Oxidative Stress Mediates the Antiproliferative Effects of Nelfinavir in Breast Cancer Cells (304 views)
Plosone (ISSN: 1932-6203, 1932-6203electronic, 1932-6203linking), 2016 Jun 9; 11(6): e0155970-e0155970.
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Paper type: Journal Article,
Impact factor: 2.806, 5-year impact factor: 3.394
Url: https://www.scopus.com/inward/record.uri?eid=2-s2.0-84976272248&doi=10.1371%2fjournal.pone.0155970&partnerID=40&md5=9dae4f658bbbd868b155cee7d8f082fe
Keywords: Antineoplastic Agents Pharmacology , Apoptosis Drug Effects , Breast Neoplasms Drug Therapy Metabolism Pathology , Cell Proliferation Drug Effects , Female , Hiv Protease Inhibitors Pharmacology , Humans , Nelfinavir Pharmacology , Oxidative Stress Drug Effects , Reactive Oxygen Species Metabolism , Tumor Cells, Cultured,
Affiliations:
*** IBB - CNR ***
Department of Translational Medical Science, University of Naples Federico II, Naples, Italy., Institute of Biostructure and Bioimaging (IBB) of the Italian National Research Council (CNR), Naples, Italy., Department of Clinical Medicine and Surgery, Breast Unit, University of Naples Federico II, Naples, Italy., Department of Emergency and Reception, Plastic Surgery Operative Unit, Hospital Center A. Cardarelli, Naples, Italy., Department of Pharmacy, University of Salerno, Salerno, Italy., Department of Medicine and Surgery, University of Salerno, Salerno, Italy., Department of Clinical Medicine and Surgery, Oncology Division, University of Naples Federico II, Naples, Italy.,
Institute of Biostructure and Bioimaging (IBB) of the Italian National Research Council (CNR), Naples, Italy.
Department of Clinical Medicine and Surgery, Breast Unit, University of Naples Federico II, Naples, Italy.
Department of Emergency and Reception, Plastic Surgery Operative Unit, Hospital Center A. Cardarelli, Naples, Italy.
Department of Pharmacy, University of Salerno, Salerno, Italy.
Department of Medicine and Surgery, University of Salerno, Salerno, Italy.
References:
Not available.
Plosone (ISSN: 1932-6203, 1932-6203electronic, 1932-6203linking), 2016 Jun 9; 11(6): e0155970-e0155970.
Export to BibTeX Export to EndNote
Paper type: Journal Article,
Impact factor: 2.806, 5-year impact factor: 3.394
Url: https://www.scopus.com/inward/record.uri?eid=2-s2.0-84976272248&doi=10.1371%2fjournal.pone.0155970&partnerID=40&md5=9dae4f658bbbd868b155cee7d8f082fe
Keywords: Antineoplastic Agents Pharmacology , Apoptosis Drug Effects , Breast Neoplasms Drug Therapy Metabolism Pathology , Cell Proliferation Drug Effects , Female , Hiv Protease Inhibitors Pharmacology , Humans , Nelfinavir Pharmacology , Oxidative Stress Drug Effects , Reactive Oxygen Species Metabolism , Tumor Cells, Cultured,
Affiliations:
*** IBB - CNR ***
Department of Translational Medical Science, University of Naples Federico II, Naples, Italy., Institute of Biostructure and Bioimaging (IBB) of the Italian National Research Council (CNR), Naples, Italy., Department of Clinical Medicine and Surgery, Breast Unit, University of Naples Federico II, Naples, Italy., Department of Emergency and Reception, Plastic Surgery Operative Unit, Hospital Center A. Cardarelli, Naples, Italy., Department of Pharmacy, University of Salerno, Salerno, Italy., Department of Medicine and Surgery, University of Salerno, Salerno, Italy., Department of Clinical Medicine and Surgery, Oncology Division, University of Naples Federico II, Naples, Italy.,
Institute of Biostructure and Bioimaging (IBB) of the Italian National Research Council (CNR), Naples, Italy.
Department of Clinical Medicine and Surgery, Breast Unit, University of Naples Federico II, Naples, Italy.
Department of Emergency and Reception, Plastic Surgery Operative Unit, Hospital Center A. Cardarelli, Naples, Italy.
Department of Pharmacy, University of Salerno, Salerno, Italy.
Department of Medicine and Surgery, University of Salerno, Salerno, Italy.
References:
Not available.
Oxidative Stress Mediates the Antiproliferative Effects of Nelfinavir in Breast Cancer Cells
The discovery of the anti-proliferative activity of nelfinavir in HIV-free models has encouraged its investigation as anticancer drug. Although the molecular mechanism by which nelfinavir exerts antitumor activity is still unknown, its effects have been related to Akt inhibition. Here we tested the effects of nelfinavir on cell proliferation, viability and death in two human breast cancer cell lines and in human normal primary breast cells. To identify the mechanism of action of nelfinavir in breast cancer, we evaluated the involvement of the Akt pathway as well as the effects of nelfinavir on reactive oxygen species (ROS) production and ROS-related enzymes activities. Nelfinavir reduced breast cancer cell viability by inducing apoptosis and necrosis, without affecting primary normal breast cells. The antitumor activity of nelfinavir was related to alterations of the cell redox state, coupled with an increase of intracellular ROS production limited to cancer cells. Nelfinavir treated tumor cells also displayed a downregulation of the Akt pathway due to disruption of the Akt-HSP90 complex, and subsequent degradation of Akt. These effects resulted to be ROS dependent, suggesting that ROS production is the primary step of nelfinavir anticancer activity. The analysis of ROS-producers and ROS-detoxifying enzymes revealed that nelfinavir-mediated ROS production was strictly linked to flavoenzymes activation. We demonstrated that ROS enhancement represents the main molecular mechanism required to induce cell death by nelfinavir in breast cancer cells, thus supporting the development of new and more potent oxidizing molecules for breast cancer therapy.
The discovery of the anti-proliferative activity of nelfinavir in HIV-free models has encouraged its investigation as anticancer drug. Although the molecular mechanism by which nelfinavir exerts antitumor activity is still unknown, its effects have been related to Akt inhibition. Here we tested the effects of nelfinavir on cell proliferation, viability and death in two human breast cancer cell lines and in human normal primary breast cells. To identify the mechanism of action of nelfinavir in breast cancer, we evaluated the involvement of the Akt pathway as well as the effects of nelfinavir on reactive oxygen species (ROS) production and ROS-related enzymes activities. Nelfinavir reduced breast cancer cell viability by inducing apoptosis and necrosis, without affecting primary normal breast cells. The antitumor activity of nelfinavir was related to alterations of the cell redox state, coupled with an increase of intracellular ROS production limited to cancer cells. Nelfinavir treated tumor cells also displayed a downregulation of the Akt pathway due to disruption of the Akt-HSP90 complex, and subsequent degradation of Akt. These effects resulted to be ROS dependent, suggesting that ROS production is the primary step of nelfinavir anticancer activity. The analysis of ROS-producers and ROS-detoxifying enzymes revealed that nelfinavir-mediated ROS production was strictly linked to flavoenzymes activation. We demonstrated that ROS enhancement represents the main molecular mechanism required to induce cell death by nelfinavir in breast cancer cells, thus supporting the development of new and more potent oxidizing molecules for breast cancer therapy.
Oxidative Stress Mediates the Antiproliferative Effects of Nelfinavir in Breast Cancer Cells
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Oxidative Stress Mediates the Antiproliferative Effects of Nelfinavir in Breast Cancer Cells
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View Export to BibTeX Export to EndNote
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View Export to BibTeX Export to EndNote
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View Export to BibTeX Export to EndNote
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View Export to BibTeX Export to EndNote
18 Records (17 excluding Abstracts).
Total impact factor: 91.136 (85.959 excluding Abstracts).
Total 5 year impact factor: 89.302 (83.942 excluding Abstracts).
Total impact factor: 91.136 (85.959 excluding Abstracts).
Total 5 year impact factor: 89.302 (83.942 excluding Abstracts).
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