Journal
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
Volume 63, Issue -, Pages 62-71Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jnutbio.2018.09.022
Keywords
Ferulic acid; Multidrug resistance; P-glycoprotein; NF-kappa B; Phosphatidyinositol 3-kinase
Funding
- Science and Engineering Research Board (SERB), Department of Science and Technology, New Delhi
- DST [SR/SO/BB-0034]
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In this study, the modulatory effect of ferulic acid on P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) was examined in KB Ch(R)8-5 resistant cells and drug-resistant tumor xenografts. We observed that ferulic acid enhanced the cytotoxicity of doxorubicin and vincristine in the P-gp overexpressing KB Ch(R)8-5 cells. Further, ferulic acid enhances the doxorubicin induced gamma H2AX foci formation and synergistically augmented doxorubicin-induced apoptotic signaling in the drug resistant cells. It has also been noticed that NF-kappa B nuclear translocation was suppressed by ferulic acid and that this response might be associated with the modulation of phosphatidyinositol 3-kinase (PI3K)/Akt/signaling pathway. We also found that ferulic acid and doxorubicin combination reduced the size of KB Ch(R)8-5 tumor xenograft by threefold as compared to doxorubicin-alone treated group. Thus, ferulic acid contributes to the reversal of the MDR through suppression of P-gp expression via the inhibition of PI3K/Akt/NF-kappa B signaling pathway. (C) 2018 Elsevier Inc. All rights reserved.
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