Multidrug resistance reversing activity of newly developed phenothiazines on P-glycoprotein (ABCB1)-related resistance of mouse T-lymphoma cells.

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.

• Authors: Gabriella Spengler, Daniella Takács, Adám Horváth, Zsuzsanna Riedl, György Hajós, Leonard Amaral, József Molnár
• Journal: Anticancer research (Anticancer Res) Vol. 34 Issue 4 Pg. 1737-41 (Apr 2014) ISSN: 1791-7530 [Electronic] Greece
• PMID: 24692704 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ATP Binding Cassette Transporter, Subfamily B
• Antineoplastic Agents
• Phenothiazines
• Rhodamine 123
• phenothiazine

Topics

• ATP Binding Cassette Transporter, Subfamily B (genetics, metabolism)
• Animals
• Antineoplastic Agents (chemistry, pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Drug Resistance, Multiple
• Drug Resistance, Neoplasm
• Gene Expression
• Lymphoma, T-Cell (genetics, metabolism)
• Mice
• Phenothiazines (chemistry, pharmacology)
• Rhodamine 123 (metabolism)