Overexpression Of ABCC1 Confers Drug Resistance To Betulin

Betulin is a lupane-type pentacyclic triterpene,which is isolatedfrom birch bark.It has a broad spectrum of biological and pharmacological properties,such as anti-inflammatory,anti-tumor,anti-viral,and anti-bacterial activity.Herein,we explored the factors that mayresult in betulin resistance,especially with respect to its interaction with ATP-binding cassette subfamily C member 1(ABCC1).ABCC1 is an important member of the ATP-binding cassette(ABC)transporter family,which is central to mediating multidrug resistance(MDR)in naturally derived anticancer agents.An MTT-based cell viability assay showed that ABCC1 overexpression has the ability to desensitize both cancer cell line and gene-transfected cell line to betulin and that this betulin-induced resistance can be antagonized by a known ABCC1 inhibitor MK571 at 25 μM.Additionally,betulin upregulates the ABCC1 protein expression level in both concentration-dependent and time-dependent manners,also blocks the transport function mediated by ABCC1.Subsequently,a high affinity score of betulin was achieved in a computational docking analysis,demonstrating a strong interaction of betulin with ABCC1.