In vitro anticancer effect of tricyclic antidepressant nortriptyline on multiple myeloma

Date

2018-01-01

Author

BİBER, Aysenur
DURUSU, Ipek Z.
Özen, Can

Metadata

Show full item record

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Item Usage Stats

98
views

0
downloads

Drug repurposing has been proved to be an effective strategy to meet the urgent need for novel anticancer agents for multiple myeloma (MM) treatment. In this work, we aimed to investigate the anticancer effect and mechanism of tricyclic antidepressant nortriptyline (NTP) on the U266 MM cell line. The in vitro inhibitory effect of NTP at various doses and time points was studied. The combination potential of cisplatin-NTP was also investigated. Cell cycle analysis and three flow cytometric apoptosis assays were performed. NTP showed dose- and time-dependent inhibitory effects on the U266 MM cell line. NTP had greater inhibitory effect than cisplatin (IC50 26 mu M vs. 40 mu M). The cisplatin-NTP combination is antagonistic. In addition to G2/M phase cell cycle arrest, NIP induced apoptosis as indicated by mitochondrial membrane potential and caspase-3 and annexin V assays. NIP has inhibitory and apoptotic effects on U266 MM cells. The cisplatin-NTP combination indicated strong antagonism, which may have significant clinical relevance since antidepressants are commonly employed in adjuvant therapy for cancer patients. Based on these findings, the therapeutic potential of NTP for MM treatment should be investigated with in-depth mechanistic studies and in vivo experiments.

Subject Keywords

Tricyclic antidepressant, Combination chemotherapy, Cancer, Apoptosis, Multiple myeloma, Cancer-cells, Combination, Cytotoxicity, Apoptosis, Growth, Glioma, Death

URI

https://hdl.handle.net/11511/30440

Journal

TURKISH JOURNAL OF BIOLOGY

DOI

https://doi.org/10.3906/biy-1802-11

Collections

Graduate School of Natural and Applied Sciences, Article

Suggestions

OpenMETU
Core

Targeting glucosylceramide synthase sensitizes imatinib-resistant chronic myeloid leukemia cells via endogenous ceramide accumulation BARAN, YUSUF; Bielawski, Jacek; Gündüz, Ufuk; Ogretmen, Besim (2011-10-01) Purpose Drug resistance presents a major obstacle for the treatment of some patients with chronic myeloid leukemia (CML). Pro-apoptotic ceramide mediates imatinib-induced apoptosis, and metabolism of ceramide by glucosylceramide synthase (GCS) activity, converting ceramide to glucosyl ceramide, might contribute to imatinib resistance. In this study, we investigated the role of ceramide metabolism by GCS in the regulation of imatinib-induced apoptosis in drug-sensitive and drug-resistant K562 and K562/IMA-0....
Dual function of programmed cell death 10 (PDCD10) in drug resistance Urfali-Mamatoglu, Cagri; Kazan, Hasan Huseyin; Gündüz, Ufuk (2018-05-01) Drug resistance, a major challenge in cancer chemotherapy, is a result of several mechanistic alterations including resistance to apoptosis. Apoptosis is a well-controlled cell death mechanism which is regulated by several signaling pathways. Alterations in structure, function, and expression pattern of the proteins involved in the regulation of apoptosis have been linked to drug resistance. Programmed Cell Death 10 (PDCD10) protein is recently associated with the regulation of cell survival and apoptosis. ...
Investigation of the Therapeutic Effects of Palbociclib Conjugated Magnetic Nanoparticles on Different Types of Breast Cancer Cell Lines Parsian, Maryam; MUTLU, PELİN; Taghavi Pourianazar, Negar; Yalcin Azarkan, Serap; Gündüz, Ufuk (2023-01-01) Introduction: Drug targeting and controlled drug release systems in cancer treatment have many advantages over conventional chemotherapy in terms of limiting systemic toxicity, side effects, and overcoming drug resistance. Methods and Results: In this paper, fabricating nanoscale delivery system composed of magnetic nanoparticles (MNPs) covered with poly-amidoamine (PAMAM) dendrimers and using its advantages were fully used to help the chemotherapeutic drug, Palbociclib, effectively reach tumors, specifical...
Half generations magnetic PAMAM dendrimers as an effective system for targeted gemcitabine delivery PARSIAN, MARYAM; Mutlu, Pelin; Yalcin, Serap; Tezcaner, Ayşen; Gündüz, Ufuk (2016-12-30) Tumor-specific delivery of anticancer drugs by magnetic nanoparticles will maximize the efficacy of the drug and minimize side effects, and reduce systemic toxicity. The magnetic core of these nanoparticles provides an advantage for selective drug targeting as they can be targeted to the tumor site and accumulated in cancer cells by means of an external magnetic field. Magnetic nanoparticles can be coated with Polyamidoamine (PAMAM) dendrimer and loaded with drugs. However, biomedical applications of PAMAM ...
Lithocholic acid conjugated mPEG-b-PCL micelles for pH responsive delivery to breast cancer cells

Isik, Gulhan; Kızıltay, Aysel; Hasırcı, Nesrin; Tezcaner, Ayşen (2022-06-10)

© 2022 Elsevier B.V.In this study, micelles composed of methoxy poly(ethylene glycol)-block-poly(ε-caprolactone) copolymer (mPEG-b-PCL), which has ionically conjugated lithocholic acid (LCA) and providing pH sensitive release of LCA in acidic media, were prepared as drug carrier devices for cancer therapy. Micelles were produced by co-solvent evaporation method at two different temperatures (60 °C and 25 °C) and coded as LCA60**M and LCA25**M, respectively). Hydrodynamic diameters were 86.9 nm and 228.2 nm,...

Citation Formats

A. BİBER, I. Z. DURUSU, and C. Özen, “In vitro anticancer effect of tricyclic antidepressant nortriptyline on multiple myeloma,” TURKISH JOURNAL OF BIOLOGY, pp. 414–421, 2018, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/30440.