title: Enhancement of complement-induced cell lysis: a novel mechanism for the anticancer effects of Hsp90 inhibitors.
abstract: Molecular chaperones (heat shock proteins, Hsp-s) play a pleiotropic role in immunological functions. Hsp-s participate in the presentation of peptide antigens, folding of several immunologically important proteins, such as the MHC, and in the maintenance of the activation-competent conformation of key signaling molecules (mostly serine/threonine and tyrosine kinases) of B and T cells activation. The most abundant cytoplasmic chaperone, Hsp90, is in the center of these processes. In recent years Hsp90 inhibitors emerged as very promising anticancer agents. Not surprisingly, Hsp90 inhibitors behave as immunosuppressants, and also cause an induction of superoxide production. Here we extend our previous data by showing the enhancement of complement-induced lysis of several types of tumor cells after Hsp90 inhibition. This novel mechanism may significantly contribute to the anticancer effects of Hsp90 inhibitors in vivo.
authors.affiliation: Department of Medical Chemistry, Semmelweis University, P.O. Box 260, H-1444 Budapest 8, Hungary.
authors.forename: Amere Subbarao
authors.initials: AS
authors.lastname: Sreedhar
authors.forename: Gábor
authors.initials: G
authors.lastname: Nardai
authors.forename: Péter
authors.initials: P
authors.lastname: Csermely
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D003165:Complement System Proteins / Q000276:immunology / Q000502:physiology*; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D019169:Jurkat Cells; D009369:Neoplasms / Q000188:drug therapy / Q000517:prevention & control*; D013481:Superoxides / Q000276:immunology / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D018841:HSP90 Heat-Shock Proteins; D007166:Immunosuppressive Agents; D013481:Superoxides; D003165:Complement System Proteins