1. Cancer Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran 2. Cancer Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran 3. Cancer Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran
Multidrug resistance (mdr) is one of the most obstacles in cancer chemotherapy. one of the main reasons that promote this phenomenon is increase expression of membrane protein pumps transferring drugs from inside the cell to outside, such as mdr1 in stomach cancer cells and bcrp in breast cancer cells. some studies have shown that furanocoumarins could enhance cytotoxicity of drugs, as they are natural compounds with lower toxicity to patients. bergapten and xanthotoxin belong to furanocoumarins family with some therapeutic effects that in present study we investigated their effects on mdr1 and bcrp protein pumps.
We studied the effect of bergapten and xanthotoxin on function of mdr1 and bcrp via flowcytometry followed by gene expression of them by real-time pcr. also, we measured protein expression of these pumps via flowcytometry. we did these investigations on epg85.257/rdb and mcf-7/mx cell lines representing excess mdr1 and bcrp pumps respectively.
The above mentioned compounds inhibited function of the pumps as well as they decreased gene expression of them. however, they did not effect on protein expression of these pumps.
Bergapten and xanthotoxin inhibited function of mdr1 and bcrp, so they enhance the concentration and cytotoxicity of cancer chemotherapy drugs in cells. they did not apply this effect through reducing protein expression, but through mistune the function of pumps. our results suggest that these compounds can be attractive candidates to be used along with chemical drugs to diminish multi-drug resistance effects.