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Title of article :
Curcumin down-regulates the multidrug-resistance mdr1b gene by inhibiting the PI3K/Akt/NFκB pathway
Author/Authors :
Choi، نويسنده , , Byeong-Hyeok and Kim، نويسنده , , Chang Gun and Lim، نويسنده , , Yoongho and Shin، نويسنده , , Soon-Young and Lee، نويسنده , , Young Han، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2008
Pages :
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Abstract :
Curcumin, a constituent of turmeric, has anti-inflammatory, anti-carcinogenic, and chemopreventive effects in several animal tumor models. The expression of P-glycoprotein (P-gp), encoded by the mdr gene, is often associated with multidrug resistance (MDR) to unrelated chemotherapeutic drugs in cancer cells. Here, we demonstrate that curcumin down-regulates P-gp expression in multidrug-resistant L1210/Adr cells. Transfection with a series of 5′-deleted constructs of the mdr1b gene promoter indicated that a proximal region between −205 and +42 of the sequence was responsible for the suppression of promoter activity by curcumin. This response might be associated with the inhibition of the phosphatidyinositol 3-kinase (PI3K)/Akt/nuclear factor-κB (NF-κB) signaling pathway by curcumin. Moreover, curcumin reversed the MDR of the L1210/Adr cells. Thus, curcumin can contribute to the reversal of the MDR phenotype, probably due to the suppression of P-gp expression via the inhibition of the PI3K/Akt/NF-κB signaling pathway.
Keywords :
Curcumin , Multidrug resistance , mdr1b gene , L1210 leukemia cell line , NF-?B , Transcription , P-GLYCOPROTEIN , Promoter activity , Phosphatidyinositol 3-kinase
Journal title :
Cancer Letters
Journal title :
Cancer Letters
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