Yulin Wang1, Yongjie Li2, Dong Shang3, Thomas Efferth4. 1. College of Pharmacy, Dalian Medical University, Dalian 116044, China. 2. Department of Chinese Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China. 3. Clinical Laboratory of Integrative Medicine, First Affiliated Hospital of Dalian Medical University, Dalian China; College of Integrative Medicine, Dalian Medical University, Dalian, China. Electronic address: shangdong@dmu.edu.cn. 4. Department of Pharmaceutical Biology, Institute of Pharmacy, Johannes Gutenberg University 55128 Mainz, Germany. Electronic address: efferth@uni-mainz.de.
Abstract
BACKGROUND: Artemisinin was isolated and identified in 1972, which was the starting point for a new era in antimalarial drug therapy. Furthermore, numerous studies have demonstrated that artemisinin and its derivatives exhibit considerable anticancer activity both in vitro, in vivo, and even in clinical Phase I/II trials. P-glycoprotein (P-gp) mediated multi-drug resistance (MDR) is one of the most serious causes of chemotherapy failure in cancer treatment. Interestingly, many artemisinin derivatives exhibit excellent ability to overcome P-gp mediated MDR and even show collateral sensitivity against MDR cancer cells. Furthermore, some artemisinin derivatives show P-gp-mediated MDR reversal activity. Therefore, the interaction between P-gp and artemisinin derivatives is important to develop novel combination treatment protocols with artemisinin derivatives and established anticancer drugs that are P-gp substrates. PURPOSE: This systematic review provides an updated overview on the interaction between artemisinin derivatives and P-gp and the effect of artemisinin derivatives on the P-gp expression level. RESULTS: Artemisinin derivatives exhibit multi-specific interactions with P-gp. The currently used artemisinin derivatives are not transported by P-gp. However, some of novel synthetized artemisinin derivatives exhibit P-gp substrate properties. Furthermore, many artemisinin derivatives act as P-gp inhibitors, which exhibit the potential to reverse MDR towards clinically used anticancer drugs. CONCLUSION: Therefore, studies on the interaction between artemisinin derivatives and P-gp provide important information for the development of novel anti-cancer artemisinin derivatives to reverse P-gp mediated MDR and for the design of rational artemisinin-based combination therapies against cancer.
BACKGROUND:Artemisinin was isolated and identified in 1972, which was the starting point for a new era in antimalarial drug therapy. Furthermore, numerous studies have demonstrated that artemisinin and its derivatives exhibit considerable anticancer activity both in vitro, in vivo, and even in clinical Phase I/II trials. P-glycoprotein (P-gp) mediated multi-drug resistance (MDR) is one of the most serious causes of chemotherapy failure in cancer treatment. Interestingly, many artemisinin derivatives exhibit excellent ability to overcome P-gp mediated MDR and even show collateral sensitivity against MDR cancer cells. Furthermore, some artemisinin derivatives show P-gp-mediated MDR reversal activity. Therefore, the interaction between P-gp and artemisinin derivatives is important to develop novel combination treatment protocols with artemisinin derivatives and established anticancer drugs that are P-gp substrates. PURPOSE: This systematic review provides an updated overview on the interaction between artemisinin derivatives and P-gp and the effect of artemisinin derivatives on the P-gp expression level. RESULTS:Artemisinin derivatives exhibit multi-specific interactions with P-gp. The currently used artemisinin derivatives are not transported by P-gp. However, some of novel synthetized artemisinin derivatives exhibit P-gp substrate properties. Furthermore, many artemisinin derivatives act as P-gp inhibitors, which exhibit the potential to reverse MDR towards clinically used anticancer drugs. CONCLUSION: Therefore, studies on the interaction between artemisinin derivatives and P-gp provide important information for the development of novel anti-cancerartemisinin derivatives to reverse P-gp mediated MDR and for the design of rational artemisinin-based combination therapies against cancer.
Authors: Tomas Koltai; Stephan Joel Reshkin; Tiago M A Carvalho; Daria Di Molfetta; Maria Raffaella Greco; Khalid Omer Alfarouk; Rosa Angela Cardone Journal: Cancers (Basel) Date: 2022-05-18 Impact factor: 6.575
Authors: Yankai Dong; Lina Liu; Jie Han; Lianqing Zhang; Yi Wang; Juan Li; Yuexiang Li; He Liu; Kun Zhou; Luyao Li; Xin Wang; Xue Shen; Meiling Zhang; Bo Zhang; Xiaofei Hu Journal: Front Med (Lausanne) Date: 2022-05-06