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Dual Regulatory Role of Cyclooxygenase and Lipoxygenase and their Products in Cell Survival and Apoptosis

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Frontiers in Bioactive Lipids

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Abstract

Aoptosis, or programmed cell death, is a genetically encoded cell suicide program defined by characteristic morphologic, biochemical, and molecular changes resulting in nonpathologic cell loss. A large number of distinct cellular phenotypes set apoptosis apart from another cell death process, i.e., necrosis.1,2 Apoptosis plays a key role in physiological processes such as embryonic development, maturation of the host immune system, and in maintaining tissue and organ homeostasis. Apoptosis has also been implicated in a variety of pathological conditions exemplified by cardiac infarction, atherosclerosis, Alzeimer’s disease and other neurodegenic diseases, HIV, tumorigenesis and tumor progression. A multitude of factors have been implicated in regulating/modulating apoptosis; these include: (i) oncogenes/tumor suppressor genes exemplified by p53, bcl-2 family (bcl-2, bcl-XL, bcl-Xb, bcl-XS, bax, BAG-1, bad, bak, Al, Mcl-1), myc, ras, abl, raf, Rb-1, and Waf-1; (ii) growth factor/growth factor receptors represented by NGF/NGF receptor, TNF-α/Fas, TGF-β/TGF receptor, IGF-1/IGF receptor, and PDGF/PDGF receptor; (iii) intracellular signal transducers such as protein kinase C, tyrosine kinases and protein phosphatases, lipid signaling molecules such as ceramide, and Ca2+; (iv) cell cycle regulators exemplified by cdc-2 and E2F; (v) reactive oxygen species; (vi) extracellular matrix regulators/signal transducers (extracellular matrix proteins such as fibronectin and transmembrane integrin receptors); (vii) specific endonucleases such as Ca2+- and Mg2+-dependent DNase; and (viii) cytoplasmic proteases typified by ICE (interleukin 1-converting enzyme) family.1-10 The major impact of apoptosis on cancer research is manifested primarily in three areas: oncogenesis, tumor homeostasis, and the mechanism of action of cytotoxic antitumor drugs.11 Most anti-tumor agents such as radiation (by generating oxygen radicals) and chemotherapeutic drugs kill tumor cells by inducing apoptosis. Likewise, development by tumor cells of resistance to these treatments is mostly a result of loss of response to apoptosis induction.1-11

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Author information

Authors and Affiliations

  1. Department of Radiation Oncology, Wayne State University, Detroit, MI, 48202, USA

    Dean G. Tang, Arthur T. Porter & Kenneth V. Honn

  2. Department of Biological Sciences, Wayne State University, Detroit, MI, 48202, USA

    John D. Taylor

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  1. Dean G. Tang
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  2. John D. Taylor
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  3. Arthur T. Porter
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  4. Kenneth V. Honn
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Editors and Affiliations

  1. The George Washington University Medical Center, Washington, D.C., USA

    Jack Y. Vanderhoek

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Tang, D.G., Taylor, J.D., Porter, A.T., Honn, K.V. (1996). Dual Regulatory Role of Cyclooxygenase and Lipoxygenase and their Products in Cell Survival and Apoptosis. In: Vanderhoek, J.Y. (eds) Frontiers in Bioactive Lipids. GWUMC Department of Biochemistry and Molecular Biology Annual Spring Symposia. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5875-0_19

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  • DOI: https://doi.org/10.1007/978-1-4615-5875-0_19

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-7694-1

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