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The drug resistance suppression induced by curcuminoids in colon cancer SW ‐480 cells is mediated by reactive oxygen species‐induced disruption of the micro RNA ‐27a‐ ZBTB 10‐ S p axis
Author(s) -
Noratto Giuliana D.,
Jutooru Indira,
Safe Stephen,
AngelMorales Gabriela,
MertensTalcott Susanne U.
Publication year - 2013
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201200609
Subject(s) - microbiology and biotechnology , multiple drug resistance , rna , rna interference , transfection , chemistry , colorectal cancer , gene expression , transcription (linguistics) , drug resistance , gene , cancer cell , cancer research , biology , cancer , biochemistry , genetics , linguistics , philosophy
Scope Mechanisms involving the curcuminoids effects in decreasing the prooncogenic specificity protein ( S p) transcription factors, and S p‐regulated genes in SW ‐480 colon cancer cells and how the multidrug resistance protein ( MDR 1) inhibition is mediated by S p suppression. Methods and results HT ‐29 and SW ‐480 colon cancer and normal CCD ‐18 C o colon fibroblast cells were treated with curcuminoids previously analyzed by HPLC . Gene and protein expression regulation were assessed by RT ‐ PCR , transfections with expression constructs, and W estern blots. Curcuminoids (2.5–10 μg/mL) suppressed preferentially the growth of SW ‐480 and HT ‐29 compared to CCD ‐18 C o cells and enhanced the anticancer activity of the chemotherapeutic drug 5‐fluorouracil due to the suppression of MDR 1. Additionally, S p1, S p3, and S p4 and S p‐regulated genes were downregulated by curcuminoids in SW ‐480 and this was accompanied by suppression of micro RNA ‐27a (mi R ‐27a) and induction of ZBTB 10, an m RNA target of mi R ‐27a and a transcriptional repressor of S p expression. This mechanism was mediated by the induction of ROS . RNA ‐interference and transfection with ZBTB 10‐expression plasmid demonstrated that MDR 1 was regulated by S p1 and S p3 and the disruption of the mi R ‐27a‐ ZBTB 10‐ S p axis. Conclusion Colon cancer treatment with curcuminoids will enhance the therapeutic effects of drugs in patients who have developed drug resistance.