Nortriptyline, a tricyclic antidepressant, induces apoptosis in U266 multiple myeloma cell line /

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2016
Biber, Ayşenur
Multiple Myeloma (MM), the second most common hematological malignancy, accounts for approximately 1% of all new cancer cases and deaths worldwide. Although the success of chemotherapy treatment has been significantly increased with the introduction of new generation drugs, bortezomib, thalidomide and lenalidomide, MM is still an incurable disease with a high rate of relapse. As exemplified by thalidomide, drug repurposing has been proved to be an effective strategy to meet the urgent need for novel anticancer agents for MM treatment. In addition to their primary clinical use for the treatment of depression, several tricyclic antidepressants (TCA) also act as potent antitumor agents. Among these, nortriptyline (NTP), was shown to have an inhibitory effect on osteosarcoma, prostate, melanoma and bladder cancer cells. In this work, we investigated the anticancer effect and mechanism of NTP on U266 MM cell line. We first studied NTP`s in vitro inhibitory effect at various doses and time points. Combination potential of cisplatin-NTP pair was also investigated as part of the potency examination. Next, cell cycle analysis was performed using propidium iodide staining which was followed by three flow cytometric apoptosis assays. NTP showed dose and time-dependent inhibitory effect on U266 MM cell line. It had greater inhibitory effect on U266 cells than cisplatin (cis) based on the calculated IC50 values (26.1 μM vs 39.8 μM). Cis-NTP combination indicated strong antagonism which may have significant clinical relevance since antidepressants are commonly employed in adjuvant therapy for cancer patients. NTP arrested U266 cells at G2/M phase. It also induced apoptosis as indicated by mitochondrial membrane potential, caspase-3 and Annexin V assays. Based on these preliminary findings, therapeutic potential of NTP for MM treatment should be investigated with in-depth mechanistic studies and in vivo experiments.

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Citation Formats
A. Biber, “Nortriptyline, a tricyclic antidepressant, induces apoptosis in U266 multiple myeloma cell line /,” M.S. - Master of Science, Middle East Technical University, 2016.