The drug resistance suppression induced by curcuminoids in colon cancer SW-480 cells is mediated by reactive oxygen species-induced disruption of the microRNA-27a-ZBTB10-Sp axis. Academic Article uri icon

abstract

  • SCOPE: Mechanisms involving the curcuminoids effects in decreasing the prooncogenic specificity protein (Sp) transcription factors, and Sp-regulated genes in SW-480 colon cancer cells and how the multidrug resistance protein (MDR1) inhibition is mediated by Sp suppression. METHODS AND RESULTS: HT-29 and SW-480 colon cancer and normal CCD-18Co 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 Western blots. Curcuminoids (2.5-10g/mL) suppressed preferentially the growth of SW-480 and HT-29 compared to CCD-18Co cells and enhanced the anticancer activity of the chemotherapeutic drug 5-fluorouracil due to the suppression of MDR1. Additionally, Sp1, Sp3, and Sp4 and Sp-regulated genes were downregulated by curcuminoids in SW-480 and this was accompanied by suppression of microRNA-27a (miR-27a) and induction of ZBTB10, an mRNA target of miR-27a and a transcriptional repressor of Sp expression. This mechanism was mediated by the induction of ROS. RNA-interference and transfection with ZBTB10-expression plasmid demonstrated that MDR1 was regulated by Sp1 and Sp3 and the disruption of the miR-27a-ZBTB10-Sp axis. CONCLUSION: Colon cancer treatment with curcuminoids will enhance the therapeutic effects of drugs in patients who have developed drug resistance.

published proceedings

  • Mol Nutr Food Res

altmetric score

  • 0.75

author list (cited authors)

  • Noratto, G. D., Jutooru, I., Safe, S., Angel-Morales, G., & Mertens-Talcott, S. U.

citation count

  • 56

complete list of authors

  • Noratto, Giuliana D||Jutooru, Indira||Safe, Stephen||Angel-Morales, Gabriela||Mertens-Talcott, Susanne U

publication date

  • March 2013

publisher