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A Benzylideneacetophenone Derivative Induces Apoptosis of Radiation-Resistant Human Breast Cancer Cells via Oxidative Stress

  • Park, Jeong Eon (School of Medicine and Institute for Nuclear Science and Technology, Jeju National University) ;
  • Piao, Mei Jing (School of Medicine and Institute for Nuclear Science and Technology, Jeju National University) ;
  • Kang, Kyoung Ah (School of Medicine and Institute for Nuclear Science and Technology, Jeju National University) ;
  • Shilnikova, Kristina (School of Medicine and Institute for Nuclear Science and Technology, Jeju National University) ;
  • Hyun, Yu Jae (School of Medicine and Institute for Nuclear Science and Technology, Jeju National University) ;
  • Oh, Sei Kwan (Department of Neuroscience, College of Medicine, Ewha Womans University) ;
  • Jeong, Yong Joo (Department of Bio and Nanochemistry, Kookmin University) ;
  • Chae, Sungwook (Aging Research Center, Korea Institute of Oriental Medicine) ;
  • Hyun, Jin Won (School of Medicine and Institute for Nuclear Science and Technology, Jeju National University)
  • Received : 2017.01.19
  • Accepted : 2017.03.09
  • Published : 2017.07.01

Abstract

Benzylideneacetophenone derivative (1E)-1-(4-hydroxy-3-methoxyphenyl) hept-1-en-3-one (JC3) elicited cytotoxic effects on MDA-MB 231 human breast cancer cells-radiation resistant cells (MDA-MB 231-RR), in a dose-dependent manner, with an $IC_{50}$ value of $6{\mu}M$ JC3. JC3-mediated apoptosis was confirmed by increase in sub-G1 cell population. JC3 disrupted the mitochondrial membrane potential, and reduced expression of anti-apoptotic B cell lymphoma-2 protein, whereas it increased expression of pro-apoptotic Bcl-2-associated X protein, leading to the cleavage of caspase-9, caspase-3 and poly (ADP-ribose) polymerase. In addition, JC3 activated mitogen-activated protein kinases, and specific inhibitors of these kinases abrogated the JC3-induced increase in apoptotic bodies. JC3 increased the level of intracellular reactive oxygen species and enhanced oxidative macromolecular damage via lipid peroxidation, protein carbonylation, and DNA strand breakage. Considering these findings, JC3 is an effective therapy against radiation-resistant human breast cancer cells.

Keywords

References

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