A Benzylideneacetophenone Derivative Induces Apoptosis of Radiation-Resistant Human Breast Cancer Cells via Oxidative Stress.
10.4062/biomolther.2017.010
- Author:
Jeong Eon PARK
1
;
Mei Jing PIAO
;
Kyoung Ah KANG
;
Kristina SHILNIKOVA
;
Yu Jae HYUN
;
Sei Kwan OH
;
Yong Joo JEONG
;
Sungwook CHAE
;
Jin Won HYUN
Author Information
1. School of Medicine and Institute for Nuclear Science and Technology, Jeju National University, Jeju 63243, Republic of Korea. jinwonh@jejunu.ac.kr
- Publication Type:Original Article
- Keywords:
Apoptosis;
Benzylideneacetophenone derivative;
Radiation resistance;
Reactive oxygen species
- MeSH:
Apoptosis*;
bcl-2-Associated X Protein;
Breast Neoplasms*;
Breast*;
Caspase 3;
Caspase 9;
Chalcone*;
DNA;
Extracellular Vesicles;
Humans*;
Lipid Peroxidation;
Membrane Potential, Mitochondrial;
Mitogen-Activated Protein Kinases;
Oxidative Stress*;
Phosphotransferases;
Protein Carbonylation;
Reactive Oxygen Species
- From:Biomolecules & Therapeutics
2017;25(4):404-410
- CountryRepublic of Korea
- Language:English
-
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 IC₅₀ value of 6 μM 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.
