Synergistic Tumoricidal Effects of Alpha-Lipoic Acid and Radiotherapy on Human Breast Cancer Cells via HMGB1.
Synergistic Tumoricidal Effects of Alpha-Lipoic Acid and Radiotherapy on Human Breast Cancer Cells via HMGB1.
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DOI：
10.4143/crt.2020.1015
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发表时间：
2021-07
影响因子：
4.6
通讯作者：
Jeong BK
中科院分区：
文献类型：
--
作者：
Choi HS;Kim JH;Jang SJ;Yun JW;Kang KM;Jeong H;Ha IB;Jeong BK
放射治疗(RT)是肿瘤治疗的主要策略之一。然而，一些癌细胞对辐射诱导的细胞死亡包括凋亡具有抵抗力。因此，需要针对不同抗肿瘤机制的替代方法，如细胞衰老。本研究旨在探讨α-硫辛酸(ALA)对辐射诱导的人乳腺癌细胞MDA-MB-231细胞死亡和衰老的协同作用。根据细胞处理的不同分为四组(对照组、ALA组、RT组和ALA+RT组)。分析细胞形态、细胞凋亡性死亡、线粒体活性氧、膜电位、细胞衰老和细胞周期。我们的数据显示，ALA与RT联合应用可显著促进细胞凋亡，表现为Annexin V染色、凋亡相关因子表达、线粒体损伤以及细胞形态改变和细胞数量减少。此外，ALA显著增强辐射诱导的细胞衰老，表现为胞浆组分HMGB1表达高于对照组，P53表达高于对照组，p38和核因子κB的激活以及G2/M细胞周期停滞。目前的研究是第一个报告显示ALA在已知对RT耐药的MDA-MB-231癌细胞中的一种新的作用模式(衰老诱导)，而不是凋亡细胞死亡。
Radiotherapy (RT) is one of main strategies of cancer treatment. However, some cancer cells are resistant to radiation-induced cell death, including apoptosis. Therefore, alternative approaches targeting different anti-tumor mechanisms such as cell senescence are required. This study aimed to investigate the synergistic effect of alpha-lipoic acid (ALA) on radiation-induced cell death and senescence in MDA-MB-231 human breast cancer cells. The cells were divided into four groups depending on the cell treatment (control, ALA, RT, and ALA+RT). Cells were analyzed for morphology, apoptotic cell death, mitochondrial reactive oxygen species, membrane potential, cellular senescence, and cell cycle. Our data showed that ALA significantly promoted apoptotic cell death when combined with RT, as reflected by Annexin V staining, expression of apoptosis-related factors, mitochondrial damages as well as cell morphological changes and reduction of cell numbers. In addition, ALA significantly enhanced radiation-induced cellular senescence, which was shown by increased HMGB1 expression in the cytosol fraction compared to the control, increased p53 expression compared to the control, activation of p38 as well as nuclear factor κB, and G2/M cell cycle arrest. The current study is the first report showing a new mode of action (senescence induction) of ALA beyond apoptotic cell death in MDA-MB-231 cancer cells known to be resistant to RT.
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DOI：
10.1146/annurev-pathol-121808-102144
发表时间：
2010
期刊：
Annual review of pathology
影响因子：
--
作者：
Coppé JP;Desprez PY;Krtolica A;Campisi J
通讯作者：
Campisi J
DOI：
10.1016/j.ijrobp.2009.12.013
发表时间：
2010-06-01
影响因子：
7
作者：
Chen, Wen-Shu;Yu, Yi-Chu;Chiu, Shu-Jun
通讯作者：
Chiu, Shu-Jun
影响因子：
5.2
作者：
Puchsaka, Punyawee;Chaotham, Chatchai;Chanvorachote, Pithi
通讯作者：
Chanvorachote, Pithi
影响因子：
3.6
作者：
Feuerecker, Benedikt;Pirsig, Sabine;Senekowitsch-Schmidtke, Reingard
通讯作者：
Senekowitsch-Schmidtke, Reingard
影响因子：
6.1
作者：
Guo C;Sun L;Chen X;Zhang D
通讯作者：
Zhang D