These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: The synthetic β-nitrostyrene derivative CYT-Rx20 induces breast cancer cell death and autophagy via ROS-mediated MEK/ERK pathway.
    Author: Hung AC, Tsai CH, Hou MF, Chang WL, Wang CH, Lee YC, Ko A, Hu SC, Chang FR, Hsieh PW, Yuan SS.
    Journal: Cancer Lett; 2016 Feb 28; 371(2):251-61. PubMed ID: 26683774.
    Abstract:
    The β-nitrostyrene family has been shown to suppress cancer cell proliferation and induce programmed cell death. However, mechanisms underlying β-nitrostyrenes remain less evaluated. Here, we synthesized a β-nitrostyrene derivative, CYT-Rx20, and characterized its anticancer effect and involving mechanisms in breast cancer. We found that CYT-Rx20 arrested breast cancer cells at G2/M phase and decreased cell viability by activating the caspase cascade, accompanying with increases of poly (ADP-ribose) polymerase (PARP) cleavage and γ-H2AX expression. On the other hand, up-regulation of Beclin-1, ATG5, and LC-3 was observed in CYT-Rx20-induced autophagy, which was evidently shown by transmission electron microscopy. In addition to these, CYT-Rx20-induced breast cancer cell death, intracellular reactive oxygen species (ROS) formation and expression of phospho-ERK1/2, Beclin-1, and LC-3 were significantly reversed in the presence of N-acetyl-l-cysteine (NAC), a thiol antioxidant. Furthermore, the cytotoxicity of CYT-Rx20 was enhanced by co-treatment with the autophagy inhibitor chloroquine or bafilomycin A1, suggesting that an incomplete autophagy process could deteriorate CYT-Rx20-induced cytotoxicity. In nude mice xenograft study, CYT-Rx20 significantly reduced orthotopic tumor growth. Immunohistochemical analysis revealed elevated expression of phospho-ERK1/2 and LC-3 in tumor tissues of the mice treated with CYT-Rx20. Together, we propose that CYT-Rx20 may have potential to be further developed into a β-nitrostyrene-based anticancer compound for the treatment of breast cancer.
    [Abstract] [Full Text] [Related] [New Search]