옛 화면은 좌우로 밀어 볼 수 있습니다.

Publications


지원과제 cPMTb
저자명 Lee DH, Hasanuzzaman MD, Kwon DH, Choi HY, Kim SM, Kim DJ, Kang DJ, Hwang TH, Kim HH, Shin HJ, Shin JG, Oh S, Lee SJ, Kim SW
학회정보 Curr Pharm Des. 24(46):5590-5597 / 2019.02
제 목 10-Phenyltriazoyl artemisinin is a novel P-glycoprotein inhibitor that suppresses the overexpression and function of P-glycoprotein.
LINK www.ncbi.nlm.nih.gov/pubmed/30799787/
게시일 2025-03-17 11:12:44
년도
내용 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; immunoblotting techniques; p-glycoprotein; paclitaxel; rifampin; triazolyl artemisinin.