The impact of redox and thiol status on the bone marrow: Pharmacological intervention strategies.
Imbalances in cancer cell redox homeostasis provide a platform for new opportunities in the development of anticancer drugs. The control of severe dose-limiting toxicities associated with redox regulation, including myelosuppression and immunosuppression, remains a challenge. Recent evidence implicates a critical role for redox regulation and thiol balance in pathways that control myeloproliferation, hematopoietic progenitor cell mobilization, and immune response. Hematopoietic stem cell (HSC) self-renewal and differentiation are dependent upon levels of intracellular reactive oxygen species (ROS) and niche microenvironments. Redox status and the equilibrium of free thiol:disulfide couples are important in modulating immune response and lymphocyte activation, proliferation and differentiation. This subject matter is the focus of the present review. The potential of redox modulating chemotherapeutics as myeloproliferative and immunomodulatory agents is also covered.
Grek
Christina L
CL
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC 29425, USA.
Townsend
Danyelle M
DM
Tew
Kenneth D
KD
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001853:Bone Marrow / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D006801:Humans; D007107:Immune System / Q000187:drug effects* / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D020011:Protective Agents / Q000627:therapeutic use*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism*
D000970:Antineoplastic Agents; D016207:Cytokines; D020011:Protective Agents; D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds; D005978:Glutathione