The antidepressant amitriptyline shows potent therapeutic activity against multiple myeloma.

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.