In:
Current Pharmaceutical Design, Bentham Science Publishers Ltd., Vol. 24, No. 46 ( 2019-04-26), p. 5590-5597
Abstract:
The effect of drugs on ATP-binding cassette transporters, especially permeabilityglycoprotein
(P-gp), is an important consideration during new anti-cancer drug development. Objective: In this context, the effects of a newly synthesized artemisinin derivative, 10-(4-phenyl-1H-1,2,3-
triazol)-artemisinin (5a), were evaluated on P-gp expression and function. Methods: Reverse transcript polymerase chain reaction and immunoblotting techniques were used to determine
the effect of 5a on P-gp expression in LS174T cells. In addition, the ability of 5a to work as either a substrate or an inhibitor of P-gp was investigated through different methods. Results: The results revealed that 5a acts as a novel P-gp inhibitor that dually suppresses the overexpression and
function of P-glycoprotein. Co-treatment of LS174T cell line, human colon adenocarcinoma cell line, with 5a and paclitaxel recovered the anticancer effect of paclitaxel by controlling the acquired drug resistance pathway. The
overexpression of P-gp induced by rifampin and paclitaxel in a colorectal cell line was suppressed by 5a which could be a novel inhibitory substrate inhibiting the transport of paclitaxel by P-gp. Conclusion: The results revealed that 5a can be classified as a type B P-gp inhibitor (with both substrate and
inhibitor activities) with an additional function of suppressing P-gp overexpression. The results might be clinically useful in the development of anticancer drugs against cancers with multidrug resistance.
Type of Medium:
Online Resource
ISSN:
1381-6128
DOI:
10.2174/1381612825666190222155700
Language:
English
Publisher:
Bentham Science Publishers Ltd.
Publication Date:
2019
SSG:
15,3
