Serotonin type-3 receptor antagonists selectively kill melanoma cells through classical apoptosis, microtubule depolymerisation, ERK activation, and NF-κB downregulation.

Cell Biology and Toxicology
Anita Barzegar-FallahS K Baird


Malignant melanoma is a highly metastatic tumour, resistant to treatment. Serotonin type-3 (5-HT3) receptor antagonists, such as tropisetron and ondansetron, are well-tolerated antiemetic drugs commonly used to prevent nausea caused by chemotherapy or radiotherapy. We investigated the anticancer effects of these drugs on melanoma cancer cell lines WM-266-4 and B16F10 with or without paclitaxel. We constructed IC50 curves and performed Chou-Talalay analysis, using data obtained with the MTT assay. Flow cytometry and fluorescent microscopy were used to examine characteristics of the cell cycle, cell death and cytoskeleton changes. Protein levels and activation were analysed by western blotting and molecular docking studies carried out. Data were analysed by one way ANOVA and post hoc testing. Ondansetron and tropisetron showed selective concentration-dependent cytotoxicity in melanoma cell lines WM-266-4 and B16F10. The effect in combination with paclitaxel was synergistic. The drugs did not cause cell cycle arrest but did promote characteristics of classical apoptosis, including accumulation of subG1 DNA, cleaved caspase-3, mitochondrial membrane permeability and phosphatidylserine exposure. As well, the cytosolic calcium level ...Continue Reading


Feb 1, 1990·Cell Calcium·M W RoeB Herman
Dec 1, 1989·Biophysical Journal·D L FarkasL M Loew
Dec 20, 1994·Proceedings of the National Academy of Sciences of the United States of America·L M LoewF S Fay
Apr 4, 1997·Journal of Molecular Biology·G JonesR Taylor
Oct 12, 2000·Scandinavian Journal of Rheumatology. Supplement·H Wolf
Oct 12, 2000·Scandinavian Journal of Rheumatology. Supplement·W Müller, T Stratz
Feb 13, 2001·The Journal of Clinical Investigation·A S Baldwin
Feb 1, 2002·The Journal of Biological Chemistry·Damu TangAlistair J Ingram
May 11, 2002·Nature Reviews. Cancer·Michael KarinZhi-Wei Li
Apr 4, 2003·Analytical Biochemistry·Donna M BarronSusan Bane
Jun 1, 2005·Biochemical Pharmacology·Laureano de la VegaBernd L Fiebich
Apr 14, 2006·Mayo Clinic Proceedings·Deborah L CumminsArjun Chanmugam
Jan 4, 2007·Cancer·Helen J GogasVernon K Sondak
Feb 23, 2007·Nature·Vanessa Gray-SchopferRichard Marais
Dec 9, 2008·Biochemical and Biophysical Research Communications·Susumu TanimuraMichiaki Kohno
Sep 8, 2009·Experimental Cell Research·Robert W JackmanSusan C Kandarian
Dec 17, 2009·European Journal of Cancer Prevention : the Official Journal of the European Cancer Prevention Organisation (ECP)·Ramin AtaeeAmin Ataee
Jul 6, 2011·The Biochemical Journal·Martin D Brand, David G Nicholls
Aug 15, 2012·Journal of Cheminformatics·Marcus D HanwellGeoffrey R Hutchison
Jan 1, 2014·Neurotoxicology·Anita Barzegar-FallahAhmad Reza Dehpour
Jun 9, 2016·MethodsX·Simon MolgaardSimon Glerup
May 8, 2018·European Journal of Medicinal Chemistry·Giuseppe La ReginaRomano Silvestri

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.


Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis