Phenothiazines and Selenocompounds: A Potential Novel Combination Therapy of Multidrug Resistant Cancer.

Abstract

BACKGROUND/AIM:

Phenothiazines constitute a versatile family of compounds in terms of biological activity, which have also gained a considerable attention in cancer research.

MATERIALS AND METHODS:

Three phenothiazines (promethazine, chlorpromazine and thioridazine) have been tested in combination with 11 active selenocompounds against MDR (ABCB1-overexpressing) mouse T-lymphoma cells to investigate their activity as combination chemotherapy and as antitumor adjuvants in vitro with a checkerboard combination assay.

RESULTS:

Seven selenocompounds showed toxicity on mouse embryonic fibroblasts, while three showed selectivity towards tumor cells. Two compounds showed synergism with all tested phenothiazines in low concentration ranges (1.46-11.25 μM). Thioridazine was the most potent among the three phenothiazines.

CONCLUSION:

Phenothiazines belonging to different generations showed different levels of adjuvant activities. All the tested phenothiazines are already approved medicines with known pharmacological and toxicity profiles, therefore, their use as adjuvants in cancer may be considered as a potential drug repurposing strategy.

• Authors: MÁriÓ GajdÁcs, MÁrta NovÉ, Ákos Csonka, Borisz Varga, Carmen SanmartÍn, Enrique DomÍnguez-Álvarez, Gabriella Spengler
• Journal: Anticancer research (Anticancer Res) Vol. 40 Issue 9 Pg. 4921-4928 (Sep 2020) ISSN: 1791-7530 [Electronic] Greece
• PMID: 32878780 (Publication Type: Journal Article)
• Copyright: Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Chemical References

• ATP Binding Cassette Transporter, Subfamily B
• Antineoplastic Agents
• Organoselenium Compounds
• Phenothiazines

Topics

• ATP Binding Cassette Transporter, Subfamily B (genetics)
• Animals
• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Cell Line, Tumor
• Dose-Response Relationship, Drug
• Drug Resistance, Multiple (drug effects, genetics)
• Drug Resistance, Neoplasm (drug effects, genetics)
• Drug Synergism
• Lymphoma, T-Cell (drug therapy, pathology)
• Mice
• Molecular Structure
• Organoselenium Compounds (chemical synthesis, chemistry, pharmacology)
• Phenothiazines (chemical synthesis, chemistry, pharmacology)