The antidepressant amitriptyline shows potent therapeutic activity against multiple myeloma

Anticancer Drugs. 2013 Sep;24(8):792-8. doi: 10.1097/CAD.0b013e3283628c21.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Amitriptyline / administration & dosage
  • Amitriptyline / pharmacology*
  • Animals
  • Antidepressive Agents, Tricyclic / administration & dosage
  • Antidepressive Agents, Tricyclic / pharmacology*
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Apoptosis / drug effects
  • Apoptosis Regulatory Proteins / metabolism
  • Boronic Acids / pharmacology
  • Bortezomib
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Female
  • Humans
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / pathology
  • Proteasome Inhibitors / pharmacology
  • Pyrazines / pharmacology
  • Time Factors
  • Tumor Burden / drug effects
  • Xenograft Model Antitumor Assays


  • Antidepressive Agents, Tricyclic
  • Antineoplastic Agents
  • Apoptosis Regulatory Proteins
  • Boronic Acids
  • Proteasome Inhibitors
  • Pyrazines
  • Amitriptyline
  • Bortezomib