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Current Pharmaceutical Design


ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

General Research Article

10-Phenyltriazoyl Artemisinin is a Novel P-glycoprotein Inhibitor that Suppresses the Overexpression and Function of P-glycoprotein

Author(s): Dong-Hwan Lee, Md. Hasanuzzaman, Daeho Kwon, Hye-Young Choi, So Myoung Kim, Dong Jin Kim, Dong Ju Kang, Tae-Ho Hwang, Hyung-Hoi Kim, Ho Jung Shin, Jae-Gook Shin, Sangtae Oh, Seokjoon Lee* and So Won Kim*

Volume 24, Issue 46, 2018

Page: [5590 - 5597] Pages: 8

DOI: 10.2174/1381612825666190222155700

Price: $65


Background: 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.

Keywords: Artemisinin, triazolyl artemisinin, p-glycoprotein, rifampin, paclitaxel, immunoblotting techniques.

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