pad

Synergistic Reversal effect quercetin & hyperthermia: doxorubicin

The synergistic reversal effect of multidrug resistance by quercetin and hyperthermia in doxorubicin-resistant human myelogenous leukemia cells

Authors: Jing Shen a; Weijing Zhang a; Jun Wu b; Yunfeng Zhu c

Affiliations: a Affiliated Hospital, Academy of Military Medical Sciences, b Beijing Institute of Biotechnology, Beijing, China c Oncology Research Institute, Affiliated Hospital, Academy of Military Medical Sciences,

Abstract Purpose: This study aimed to evaluate the multidrug resistance (MDR) reversal activity of quercetin (Que) in combination with hyperthermia (HT) in human myelogenous leukemia cells K562/A.

Methods: The cytotoxicity of Que alone and the effect of Que and HT to doxorubicin (Dox) cytotoxicity were determined using MTT assay in K562 and K562/A cells. K562/A cells was heated with or without Que pretreatment, and the protein and mRNA levels of heat shock protein 70 (HSP70) and P-glycoprotein (P-gp) were determined by flow cytometry (FCM) and RT-PCR, respectively.

Intracellular accumulation of Dox, cell cycle and apoptosis were monitored with FCM.

Results: Que alone inhibited cell growth in a dose-dependent manner in K562 and K562/A cells. Either Que or HT alone had a weak reversal effect on Dox resistance, however, combination HT and Que showed a much more significant reversal effect on Dox resistance (reverse fold 9.49).

The elevated protein expression and mRNA level of HSP70 and P-gp in response to HT were inhibited by Que. Pretreatment with Que caused the cells to accumulate Dox 8.3-fold higher than in control cells.

In addition, Que induced apoptosis and G2/M arrest in a dose-dependent manner, and the combination of Que and HT was found to have a synergistic efeect on apoptosis.

Conclusions: Que pretreatment could significantly inhance the MDR reversal activity of HT in resistant cell line, by sensitizing the cell to reversing MDR activity of HT.

DOI: 10.1080/02656730701843109

International Journal of Hyperthermia, Volume 24, Issue 2 2008 , pages 151 - 159

First Published on: 14 January 2008

Remember we are NOT Doctors and have NO medical training.

This site is like an Encylopedia - there are many pages, many links on many topics.

Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.