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- Title
Piperlongumine induces cell death through ROS-mediated CHOP activation and potentiates TRAIL-induced cell death in breast cancer cells.
- Authors
Jin, Hyeon-Ok; Lee, Yun-Han; Park, Jin-Ah; Lee, Ha-Na; Kim, Jin-Hee; Kim, Ji-Young; Kim, BoRa; Hong, Sung-Eun; Kim, Hyun-Ah; Kim, Eun-Kyu; Noh, Woo; Kim, Jong-Il; Chang, Yoon; Hong, Seok-Il; Hong, Young-Jun; Park, In-Chul; Lee, Jin
- Abstract
Purpose: Piperlongumine (PL) has been shown to selectively induce apoptotic cell death in cancer cells via reactive oxygen species (ROS) accumulation. In this study, we characterized a molecular mechanism for PL-induced cell death. Methods: Cell viability and cell death were assessed by MTT assay and Annexin V-FITC/PI staining, respectively. ROS generation was measured using the HDCFDA. Small interfering RNA (siRNA) was used for suppressing gene expression. The mRNA and protein expression were analyzed by RT-PCR and Western blot analysis, respectively. Results: We found that PL promotes C/EBP homologous protein (CHOP) induction, which leads to the up-regulation of its targets Bim and DR5. Pretreatment with the ROS scavenger N-acetyl-cysteine abolishes the PL-induced up-regulation of CHOP and its target genes, suggesting an essential role for ROS in PL-induced CHOP activation. The down-regulation of CHOP or Bim with siRNA efficiently attenuates PL-induced cell death, suggesting a critical role for CHOP in this cell death. Furthermore, PL potentiates TRAIL-induced cytotoxicity in breast cancer cells by upregulating DR5, as DR5 knockdown abolished the sensitizing effect of PL on TRAIL responses. Conclusions: Overall, our data suggest a new mechanism for the PL-induced cell death in which ROS mediates CHOP activation, and combination treatment with PL and TRAIL could be a potential strategy for breast cancer therapy.
- Subjects
INDIAN long pepper; CELL death; REACTIVE oxygen species; CCAAT enhancer binding proteins; TRANCE protein; APOPTOSIS; BREAST cancer treatment; THERAPEUTICS
- Publication
Journal of Cancer Research & Clinical Oncology, 2014, Vol 140, Issue 12, p2039
- ISSN
0171-5216
- Publication type
Article
- DOI
10.1007/s00432-014-1777-1