title: The antidepressant amitriptyline shows potent therapeutic activity against multiple myeloma.
abstract: Our previous study indicated that the antidepressant amitriptyline showed potent activity in inducing multiple myeloma (MM) cell apoptosis in vitro. In the present study, we further showed that amitriptyline was active against MM in vivo. Oral administration of amitriptyline significantly decreased tumor growth in two MM xenograft models derived from murine and human MM cells, respectively. Molecular pathological analysis showed that amitriptyline induced p53, activated caspase-3, and decreased antiapoptotic Bcl-2 and Mcl-1 in tumor tissues. Amitriptyline also significantly extended the survival period of MM-tumor-bearing mice. In the in-vitro study, we also found that amitriptyline synergistically induced MM cell apoptosis in combination with bortezomib, the most potent anti-MM agent. Because amitriptyline has been proposed to control cancer-associated pain, depression, and anxiety, proper application of amitriptyline will benefit MM patients.
authors.affiliation: Laboratory of Targeted Drug Discovery, Cyrus Tang Hematology Center, School of Pharmacy, Soochow University, Suzhou, People's Republic of China.
authors.forename: Zubin
authors.initials: Z
authors.lastname: Zhang
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Du
authors.forename: Changzhen
authors.initials: C
authors.lastname: Zhao
authors.forename: Biyin
authors.initials: B
authors.lastname: Cao
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhao
authors.forename: Xinliang
authors.initials: X
authors.lastname: Mao
mesh_terms: D000284:Administration, Oral; D000639:Amitriptyline / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001897:Boronic Acids / Q000494:pharmacology; D000069286:Bortezomib; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology; D061988:Proteasome Inhibitors / Q000494:pharmacology; D011719:Pyrazines / Q000494:pharmacology; D013997:Time Factors; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000929:Antidepressive Agents, Tricyclic; D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D001897:Boronic Acids; D061988:Proteasome Inhibitors; D011719:Pyrazines; D000639:Amitriptyline; D000069286:Bortezomib