Abstract
Background: Phenothiazines have anticancer properties and are able to reverse the multidrug resistance of neoplastic cells by inhibiting the ATP-binding cassette, sub-family B (MDR/TAP), member 1 protein (ABCB1 or P-glycoprotein) activity. Materials and Methods: A series of new phenothiazine derivatives was investigated regarding their ABCB1-modulating effect on multidrug resistant mouse T-lymphoma cells by rhodamine 123 accumulation assay and real-time ethidium bromide accumulation assay. Results: The phenothiazine derivatives exhibited a potent anticancer effect on the parental cell line and on its multidrug-resistant mouse T-lymphoma subline overexpressing the ABCB1 transporter. The inhibition of the ABCB1 transporter in the presence of the newly-developed phenothiazines was greater than that for the known ABCB1 inhibitors thioridazine and verapamil. Conclusion: Based on the chemical structures and biological activity, compounds with bivalent sulfur atom in the phenothiazine ring demonstrated marked ABCB1-modulating effect, however, other derivatives with halogen or amide substitutions were ineffective.
- Phenothiazines
- multidrug resistance
- P-glycoprotein
- ABCB1
- ATP-binding cassette protein B1
- rhodamine 123
- ethidium bromide
- thioridazine
- verapamil
- mouse T-lymphoma cell lines
- Received November 6, 2013.
- Revision received January 7, 2014.
- Accepted January 10, 2014.
- Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved