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

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.


Molecular characterization of the effects of valdecoxib on colon cancer cell lines (ht29 & sw620) using ATR-FTIR spectroscopy
İnan Genç, Aysun; Severcan, Feride; Banerjee, Sreeparna; Department of Biochemistry (2014)
Colorectal cancer is the third most common malignancy and the fourth most frequent cause of cancer deaths worldwide, with 945,000 estimated new cases and 492,000 deaths per year in industrialized countries. Chronic inflammation of the bowel is associated with increased levels of pro-inflammatory cytokines and the increased signaling, which plays important roles in the development of carcinoma. During chronic inflammation COX-2 levels are dramatically increased which is the main enzyme in the arachidonic aci...
Structural mapping and network analysis of patient-specific mutations in glioblastoma
Kaya, Tuğba; Tunçbağ, Nurcan; Doğan, Tunca; Department of Bioinformatics (2018)
Cancer is one of the most common cause of death worldwide. It occurs as a result of a collection of somatic deviations from normal state. Therefore, many efforts have been invested to profile mutations in different types of tumors; such as, the Cancer Genome Atlas (TCGA) which deposits multiple omic data for more than 11,000 tumor samples. In this thesis, we present a pipeline which retrieves patient-specific mutation data in Glioblastoma from TCGA, maps these mutations on the protein structures in Protein ...
Cancer modeling via biologically validated genes
Karakelle, Barış Su; Purutçuoğlu Gazi, Vilda; Ürün, Yüksel (2017-05-10)
The cancer disease is the second most common disease type seen after the frequency of the cardiovascular diseases. The frequency of this genetic disease changes with respect to the gender. Accordingly, the gynecological cancer, which covers ovarian, endometrial or cervical cancer, is the second most common cancer type in women after the breast cancer. Similar to other cancer types, the gynecological cancer is the system disease, meaning that the malfunctions and mutations in the gene regulatory ...
Synthesis of poly (dl-lactic-co-glycolic acid) coated magnetic nanoparticles for anti-cancer drug delivery
Tansık, Gülistan; Gündüz, Ufuk; Department of Biology (2012)
One of the main problems of current cancer chemotherapy is the lack of selectivity of anti-cancer drugs to tumor cells which leads to systemic toxicity and adverse side effects. In order to overcome these limitations, researches on controlled drug delivery systems have gained much attention. Nanoscale based drug delivery systems provide tumor targeting. Among many types of nanocarriers, superparamagnetic nanoparticles with their biocompatible polymer coatings can be targeted to an intented site by an extern...
Characterization of liposomal celecoxib formulation as a drug delivery system in colorectal cancer cell lines
Erdoğ, Aslı; Banerjee, Sreeparna; Department of Biotechnology (2012)
Colorectal carcinoma (CRC) is one of the most common cancers and is the leading cause of cancer deaths in much of the developed world. Owing to the high incidence of drug resistance and potential toxic effects of chemotherapy drugs, much research is currently underway to design better strategies for smart drug delivery systems. Cyclooxygenase-2 (COX-2) pathway is associated with poor prognosis in colon carcinomas. The selective COX-2 inhibitor drug Celecoxib (CLX) has been shown to posses COX-2 independent ...
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.