Glycoprotein (P-gp) is an important protein of the cell membrane that pumps many foreign substances out of cells. Importantly, P-gp is an ATP-dependent efflux pump with broad substrate specificity. Besides, It exists in animals, fungi, and bacteria, and it likely evolved as a defense mechanism against harmful substances. Particularly, P-gp is a glycoprotein and P-gp is a well-characterized ABC-transporter (which transports a wide variety of substrates across extra- and intracellular membranes) of the MDR/TAP subfamily.
Some cancer cells also express large amounts of P-gp, further amplifying that effect and rendering these cancers multidrug resistant. Besides, P-gp is one of the major contributors to multidrug resistance (MDR), as it protects MDR cancer cells by effluxing cytotoxic drugs. Moreover, natural products are considered as an alternative source of drugs to fight MDR cancer. So, Here we will introduce a natural product as a P-gp inhibitor for cancer.
Coleon-U-quinone is a potent P-gp inhibitor, with anti-cancer activity.
Coleon-U-quinone is an abietane diterpene that is isolated from Phacelia mutabilis by bio-guided chromatographic fractionation. Besides, Coleon-U-quinone (0-50 µM; 72 h) inhibits the cell viability with IC50 values of 22.96, 20.37, 44.13 µM against NCI-H460, NCI-H460/R and MRC-5 cells. Moreover, Coleon-U-quinone (1, 2, 5 µM) reverses the resistance to Doxorubicin in NCI-H460/R cells with IC50values of 0.565 μM, 0.482 μM and 0.217 μM at 1 μM, 2 μM and 5 μM, respectively. In addition, Coleon-U-quinone (5, 10 µM; 30 min, 72 h) diterpenoids stimulated P-gp activity in a direct interaction after application for 30 min, longer exposure leads to decreased activity of P-gp.
All in all, Coleon-U-quinone is a potent P-gp inhibitor. It inhibits P-glycoprotein (P-gp) activity and reverts doxorubicin (DOX) resistance.
Reference：
[1] Ntungwe EN, et al. ACS Med Chem Lett. 2022 Mar 11;13(4):674-680.