title: Dyclonine enhances the cytotoxic effect of proteasome inhibitor bortezomib in multiple myeloma cells.
abstract: The proteasome has become an important target for cancer therapy with the approval of bortezomib for the treatment of relapsed/refractory multiple myeloma (MM). However, numerous patients with MM do not respond to bortezomib and those responding initially often acquire resistance. Recent clinical studies have also demonstrated that bortezomib is also inefficacious in the treatment of other types of cancer. Therefore, it is imperative to develop novel approaches and agents for proteasome-targeting cancer therapy. In the present study, it was revealed that dyclonine, a major component of the cough droplets Sucrets, markedly enhances the cytotoxic effects of bortezomib and minimizes drug resistance in MM cells. It was demonstrated that a combination of bortezomib and dyclonine markedly induced apoptosis of MM cells. The present study suggests a novel therapeutic use of an over‑the‑counter medicine for the treatment of MM.
authors.affiliation: Karmanos Cancer Institute, Department of Oncology and Pathology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
authors.forename: Donghong
authors.initials: D
authors.lastname: Ju
authors.affiliation: Karmanos Cancer Institute, Department of Oncology and Pathology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
authors.forename: Youming
authors.initials: Y
authors.lastname: Xie
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001897:Boronic Acids / Q000494:pharmacology*; D000069286:Bortezomib; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy*; D011427:Propiophenones / Q000494:pharmacology*; D061988:Proteasome Inhibitors / Q000494:pharmacology*; D011719:Pyrazines / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D011427:Propiophenones; D061988:Proteasome Inhibitors; D011719:Pyrazines; C100063:dyclonine; D000069286:Bortezomib