title: Tris DBA palladium overcomes hypoxia-mediated drug resistance in multiple myeloma.
abstract: Despite recent progress in novel and targeted therapies, multiple myeloma (MM) remains a therapeutically challenging incurable disease. The regulation of important cellular processes and its link to cancer presented Src as an attractive target for MM. We suggest a novel strategy to improve the treatment of MM and overcome the drug resistance for the current therapeutic agents by specific inhibition of Src in MM cells by Tris (Dibenzylideneacetone) dipalladium (Tris DBA). Tris DBA reduces proliferation, induces G1 arrest and apoptosis in MM cells. Tris DBA showed additive effect with proteasome inhibitors reducing proliferation, cell cycle signaling, and increasing apoptosis more than each drug alone. Tris DBA overcame hypoxia-induced effects such as enhanced chemotaxis or drug resistance to proteasome inhibitors by inhibition of HIF1α expression. Moreover, we found that Tris DBA is an effective anti-myeloma agent alone or in combination with other targeted drugs and that it reverses hypoxia-induced drug resistance in myeloma.
authors.affiliation: a Department of Radiation Oncology , Cancer Biology Division, Washington University in Saint Louis School of Medicine , St. Louis , MO , USA.
authors.forename: Pilar
authors.initials: P
authors.lastname: de la Puente
authors.affiliation: a Department of Radiation Oncology , Cancer Biology Division, Washington University in Saint Louis School of Medicine , St. Louis , MO , USA.
authors.forename: Feda
authors.initials: F
authors.lastname: Azab
authors.affiliation: a Department of Radiation Oncology , Cancer Biology Division, Washington University in Saint Louis School of Medicine , St. Louis , MO , USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Muz
authors.affiliation: a Department of Radiation Oncology , Cancer Biology Division, Washington University in Saint Louis School of Medicine , St. Louis , MO , USA.
authors.forename: Micah
authors.initials: M
authors.lastname: Luderer
authors.affiliation: b Department of Dermatology , Emory University School of Medicine , Atlanta , GA , USA.|c Atlanta Veterans Administration Health Center , Atlanta , GA , USA.
authors.forename: Jack
authors.initials: J
authors.lastname: Arbiser
authors.affiliation: a Department of Radiation Oncology , Cancer Biology Division, Washington University in Saint Louis School of Medicine , St. Louis , MO , USA.
authors.forename: Abdel Kareem
authors.initials: AK
authors.lastname: Azab
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D009101:Multiple Myeloma / Q000188:drug therapy / Q000378:metabolism*; D009942:Organometallic Compounds / Q000494:pharmacology*; D061988:Proteasome Inhibitors / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D061988:Proteasome Inhibitors; C532099:tris(dibenzylideneacetone)dipalladium
keywords: Src; Tris DBA; drug resistance; hypoxia; multiple myeloma