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

被引：12

作者：

Park, Jeong Eon ^{[1
,2
]}

Piao, Mei Jing ^{[1
,2
]}

Kang, Kyoung Ah ^{[1
,2
]}

Shilnikova, Kristina ^{[1
,2
]}

Hyun, Yu Jae ^{[1
,2
]}

Oh, Sei Kwan ^{[3
]}

Jeong, Yong Joo ^{[4
]}

Chae, Sungwook ^{[5
]}

Hyun, Jin Won ^{[1
,2
]}

机构：

[1] Jeju Natl Univ, Sch Med, Jeju 63243, South Korea

[2] Jeju Natl Univ, Inst Nucl Sci & Technol, Jeju 63243, South Korea

[3] Ewha Womans Univ, Dept Neurosci, Coll Med, Seoul 03760, South Korea

[4] Kookmin Univ, Dept Bio & Nanochem, Seoul 02707, South Korea

[5] Korea Inst Oriental Med, Aging Res Ctr, Daejeon 34054, South Korea

来源：

BIOMOLECULES & THERAPEUTICS | 2017年 / 25卷 / 04期

基金：

新加坡国家研究基金会;

关键词：

Apoptosis; Benzylideneacetophenone derivative; Radiation' resistance; Reactive oxygen species; PROSTATE-CANCER; DEATH; RADIOSENSITIZER; ACTIVATION; AUTOPHAGY; PATHWAYS; THERAPY;

D O I：

10.4062/biomolther.2017.010

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 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,

引用

页码：404 / 410

页数：7

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