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

• Published in: Biomolecules & therapeutics Vol. 25; no. 4; pp. 404 - 410
• Main Authors: Park, Jeong Eon, Piao, Mei Jing, Kang, Kyoung Ah, Shilnikova, Kristina, Hyun, Yu Jae, Oh, Sei Kwan, Jeong, Yong Joo, Chae, Sungwook, Hyun, Jin Won
• Format: Journal Article
• Language: Korean
• Published: 한국응용약물학회 01.07.2017
• Subjects: Apoptosis; Benzylideneacetophenone derivative; Radiation resistance; Reactive oxygen species; Radiation resistance; Benzylideneacetophenone derivative; Reactive oxygen species; Apoptosis
• ISSN: 1976-9148; 2005-4483

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.