1. Department of Biology,Science and Research Branch,Islamic Azad University,Tehran,Iran 2. Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; 3. Department of Biology,Science and Research Branch,Islamic Azad University,Tehran,Iran
Abstract
Introduction
: multidrug resistance (mdr) in tumor cells is still a big challenge in cancer treatment. therefore, identification of safe and effective mdr reversing compounds with minimal side effects is an important approach in cancer treatment. here, we investigated the role and potential mechanisms of quercetin in doxorubicin (dox) resistant human myelogenous leukemia (k562/dox) cells.
Methods
The effect of doxorubicin on cell viability following treatment with quercetin was evaluated using trypan blue and mtt assays. rhodamine123 (rh123) assay was used to determine the activity of common drug efflux membrane transporters p-glycoprotein (p-gp). pten mrna/protein expression levels were measured by quantitative reverse transcription polymerase chain reaction (qrt-pcr) and western blot analyses. annexin-v/fitc assay was also employed to investigate apoptosis
Results
Quercetin considerably enhanced the cytotoxicity of dox. quercetin also significantly down-regulated p-gp expression and activity in k562/dox cells and reduced mdr through elevation of intracellular dox in cells. furthermore, upon quercetin treatment, pten expression could be restored in k562/dox cells
Conclusion
Quercetin could reverse mdr by inducing pten and ppar/pten signaling pathway. these findings suggest that targeting pparγ might serve as an effective approach for circumventing mdr in chemotherapy of cancerous patients
