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Breast Cancer
Synergistic Tumoricidal Effects of Alpha-Lipoic Acid and Radiotherapy on Human Breast Cancer Cells via HMGB1
Hoon Sik Choi, Jin Hyun Kim, Si Jung Jang, Jeong Won Yun, Ki Mun Kang, Hojin Jeong, In Bong Ha, Bae Kwon Jeong
Cancer Res Treat. 2021;53(3):685-694.   Published online December 15, 2020
DOI: https://doi.org/10.4143/crt.2020.1015
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
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.
Materials and Methods
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.
Results
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 кB, and G2/M cell cycle arrest.
Conclusion
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.

Citations

Citations to this article as recorded by  
  • Alpha-Lipoic Acid Modulates Melanoma Survival Networks via ER Stress Induction, Mitochondrial Apoptosis, and Kinase Pathway Suppression in B16F10 Cells
    Ömer Kokaçya, Percin Pazarci, Halil Mahir Kaplan
    Current Issues in Molecular Biology.2026; 48(7): 690.     CrossRef
  • Osthole promotes cell senescence-like phenotype to enhance radiosensitivity in non-small cell lung carcinoma possibly through modulating the Sirt1/NF-κB pathway
    Yan Li, Lianhai Miao, Zhiyong Yang, Wei Liang
    Molecular & Cellular Toxicology.2026;[Epub]     CrossRef
  • Prooxidant state in anticancer drugs and prospect use of mitochondrial cofactors and anti-inflammatory agents in cancer prevention
    Giovanni Pagano, Alex Lyakhovich, Philippe J. Thomas, Federico V. Pallardó Catalayud, Luca Tiano, Adriana Zatterale, Marco Trifuoggi
    Inflammopharmacology.2025; 33(2): 431.     CrossRef
  • Exploring the role and application of mitochondria in radiation therapy
    Yi Ding, Wang Jing, Zhichao Kang, Zhe Yang
    Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease.2025; 1871(3): 167623.     CrossRef
  • Anticancer effects of alpha-lipoic acid, a potent organosulfur compound by modulating matrix metalloproteinases and apoptotic markers in osteosarcoma MG-63 cells
    Abdolreza Ahmadi, Fatemehsadat Hosseini, Mehdi Rostami, Mohammad Soukhtanloo
    The Journal of Steroid Biochemistry and Molecular Biology.2025; 247: 106664.     CrossRef
  • Regulation of cellular senescence in tumor progression and therapeutic targeting: mechanisms and pathways
    Bowei Liu, Zhigang Peng, Hao Zhang, Nan Zhang, Zaoqu Liu, Zhiwei Xia, Shaorong Huang, Peng Luo, Quan Cheng
    Molecular Cancer.2025;[Epub]     CrossRef
  • A narrative literature review about alpha‐lipoic acid role in dry eye and ocular surface disease
    Antonio J. Mateo Orobia, José Manuel Benítez del Castillo, Margarita Calonge, Christophe Baudouin, Marc Labetoulle
    Acta Ophthalmologica.2025;[Epub]     CrossRef
  • Possible mechanisms underlying the neuroprotective effects of gold nanoparticles and alpha-lipoic acid mixture on brain damage induced by radiation: A subacute study in rats
    Noha F. Abdelkader, Ahmed I. El-Batal, Yara M. Amin, Asrar M. Hawas, Seham H.M. Hassan, Nihad I. Eid
    Journal of Drug Delivery Science and Technology.2025; 109: 106977.     CrossRef
  • Alpha lipoic acid modulates metabolic reprogramming in breast cancer stem cells enriched 3D spheroids by targeting phosphoinositide 3-kinase: In silico and in vitro insights
    Bandana Chakravarti, Manendra Singh Tomar, Faizan Abul Qais, Sana Raza, K.M. Abdullah, Gunjan Sharma, Archana Tewari, Abhishek Yadav, Pratima Gupta, Naibedya Chattopadhyay, Ashutosh Shrivastava, Rohit Anthony Sinha, Jawed Akhtar Siddiqui
    Biomedicine & Pharmacotherapy.2025; 187: 118121.     CrossRef
  • Alfa-Linolenik Asitin Apoptotik Etkileri
    Perçin PAZARCI
    Ağrı Tıp Fakültesi Dergisi.2024; 2(1): 46.     CrossRef
  • Silver anchored g-C3N4/CNT nanocomposites modified glassy carbon electrode for the detection of α-lipoic acid in pharmaceutical products
    J. Amarnath, S. Meenakshi, J. Kalaiyarasi, S. Surendhiran, K.S. Balu, A. Karthik, B. Kalpana
    Inorganic Chemistry Communications.2024; 162: 112251.     CrossRef
  • Anti-cancer effects of alpha lipoic acid, cisplatin and paclitaxel combination in the OVCAR-3 ovarian adenocarcinoma cell line
    Hatice Şiyzen Çoban, Nazlı Çil, Elif Önder, Gülçin Abban Mete
    Molecular Biology Reports.2024;[Epub]     CrossRef
  • Protein lipoylation: mitochondria, cuproptosis, and beyond
    Cheng-Han Lin, Yeh Chin, Ming Zhou, Robert W. Sobol, Mien-Chie Hung, Ming Tan
    Trends in Biochemical Sciences.2024; 49(8): 729.     CrossRef
  • The Chemoprotective Potentials of Alpha-lipoic Acid against Cisplatin-induced Ototoxicity: A Systematic Review
    Ghaidaa Raheem Lateef Al-Awsi, Uzma Arshed, Anam Arif, Andrés Alexis Ramírez-Coronel, Muataz S. Alhassan, Yasser Fakri Mustafa, Ferry Fadzlul Rahman, Rahman S. Zabibah, Jitendra Gupta, Muhammad Shahid Iqbal, Acim Heri Iswanto, Bagher Farhood
    Current Medicinal Chemistry.2024; 31(23): 3588.     CrossRef
  • The Antioxidant and HDAC-Inhibitor α-Lipoic Acid Is Synergistic with Exemestane in Estrogen Receptor-Positive Breast Cancer Cells
    Laura S. Pradel, Yu-Lin Ho, Holger Gohlke, Matthias U. Kassack
    International Journal of Molecular Sciences.2024; 25(15): 8455.     CrossRef
  • Arginine-solubilized lipoic acid-induced β-sheets of silk fibroin-strengthened hydrogel for postoperative rehabilitation of breast cancer
    Zhuodan Zhang, Yi Xia, Xinyi Li, Qian Zhang, Yuanhao Wu, Chunyan Cui, Jianfeng Liu, Wenguang Liu
    Bioactive Materials.2024; 40: 667.     CrossRef
  • Comprehensive review of drug-mediated ICD inhibition of breast cancer: mechanism, status, and prospects
    Yang Wang, Rui Yang, Ying Xie, Xi-Qiu Zhou, Jian-Feng Yang, You-Yang Shi, Sheng Liu
    Clinical and Experimental Medicine.2024;[Epub]     CrossRef
  • Combination of Alpha-Lipoic Acid and Auraptene Induces Apoptosis and Prevents Proliferation of the Human U-87 Glioblastoma Cells
    Azam Izadi, Asie Sadeghi, Mohammad Jalili-Nik, Farshad Mirzavi, Amir R. Afshari, Mohammad Soukhtanloo
    Revista Brasileira de Farmacognosia.2023; 33(6): 1177.     CrossRef
  • Alpha-Lipoic Acid Reduces Cell Growth, Inhibits Autophagy, and Counteracts Prostate Cancer Cell Migration and Invasion: Evidence from In Vitro Studies
    Sabrina Bossio, Anna Perri, Raffaella Gallo, Anna De Bartolo, Vittoria Rago, Daniele La Russa, Michele Di Dio, Sandro La Vignera, Aldo E. Calogero, Giovanni Vitale, Antonio Aversa
    International Journal of Molecular Sciences.2023; 24(23): 17111.     CrossRef
  • The potential health benefits of aloin from genus Aloe
    Jianbin Xiao, Siyuan Chen, Youqiang Chen, Jingqian Su
    Phytotherapy Research.2022; 36(2): 873.     CrossRef
  • Cellular senescence signaling in cancer: A novel therapeutic target to combat human malignancies
    Sajad Fakhri, Seyed Zachariah Moradi, Lindsay K. DeLiberto, Anupam Bishayee
    Biochemical Pharmacology.2022; 199: 114989.     CrossRef
  • Complementary and Alternative Therapies in Oncology
    Agnieszka Dawczak-Dębicka, Joanna Kufel-Grabowska, Mikołaj Bartoszkiewicz, Adrian Perdyan, Jacek Jassem
    International Journal of Environmental Research and Public Health.2022; 19(9): 5071.     CrossRef
  • Alpha-lipoic acid impedes myocardial ischemia-reperfusion injury, myocardial apoptosis, and oxidative stress by regulating HMGB1 expression
    Bingcai Qi, Yue Zheng, Wenqing Gao, Zhenchang Qi, Yijie Gong, Yanwu Liu, Yuchao Wang, Xian Cheng, Meng Ning, Yuheng Lang, Jianyu Feng, Tong Li
    European Journal of Pharmacology.2022; 933: 175295.     CrossRef
  • Anticancer Effect of Benzimidazole Derivatives, Especially Mebendazole, on Triple-Negative Breast Cancer (TNBC) and Radiotherapy-Resistant TNBC In Vivo and In Vitro
    Hoon Sik Choi, Young Shin Ko, Hana Jin, Ki Mun Kang, In Bong Ha, Hojin Jeong, Haa-Na Song, Hye Jung Kim, Bae Kwon Jeong
    Molecules.2021; 26(17): 5118.     CrossRef
  • Drug Repositioning and Subgroup Discovery for Precision Medicine Implementation in Triple Negative Breast Cancer
    Zainab Al-Taie, Mark Hannink, Jonathan Mitchem, Christos Papageorgiou, Chi-Ren Shyu
    Cancers.2021; 13(24): 6278.     CrossRef
  • 14,701 View
  • 257 Download
  • 26 Web of Science
  • 25 Crossref
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Gastrointestinal cancer
Tumor Control and Overall Survival after Stereotactic Body Radiotherapy for Pulmonary Oligometastases from Colorectal Cancer: A Meta-Analysis
Hoon Sik Choi, Bae Kwon Jeong, Ki Mun Kang, Hojin Jeong, Jin Ho Song, In Bong Ha, Oh-Young Kwon
Cancer Res Treat. 2020;52(4):1188-1198.   Published online July 21, 2020
DOI: https://doi.org/10.4143/crt.2020.402
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
In pulmonary oligometastases from colorectal cancer (POM-CRC), the primarily recommended local therapy is metastasectomy. Stereotactic body radiotherapy (SBRT) is another local therapy modality that is considered as an alternative option in patients who cannot undergo surgery. The purpose of this meta-analysis is to demonstrate the effects of SBRT on POM-CRC by integrating the relevant studies.
Materials and Methods
The authors explored MEDLINE, EMBASE, Cochrane Library, Web of Science, and SCOPUS, and selected studies including patients treated with SBRT for POM-CRC and availability of local control (LC) or overall survival (OS) rate. In this meta-analysis, the effect of SBRT was presented in the form of the LC and OS rates for 1, 2, 3, and 5 years after SBRT as pooled estimates, and the frequency of pulmonary toxicity of grade 3 or higher after SBRT (PTG3-SBRT).
Results
Fourteen full texts among the searched 4,984 studies were the objects of this meta-analysis. The overall number of POM-CRC patients was 495 as per the integration of 14 studies. The pooled estimate LC rate at 1, 2, 3, and 5 years after SBRT was 81.0%, 71.5%, 56.0%, and 61.8%, and the OS rate was 86.9%, 70.1%, 57.9%, and 43.0%, respectively. The LC and OS rates gradually declined until 3 years after SBRT in a similar pattern. Among the 14 studies, only two studies reported PTG3-SBRT as 2.2% and 10.8%, respectively.
Conclusion
For POM-CRC, SBRT is an ablative therapy with a benefit on LC and OS rates and less adverse effects on the lung.

Citations

Citations to this article as recorded by  
  • Therapeutic approaches to pulmonary metastases in colorectal cancer
    I. Yu. Kokhanovskaia, A. S. Fatyanova, E. A. Tarabrin, I. V. Reshetov
    Research and Practical Medicine Journal.2025; 12(3): 61.     CrossRef
  • Treatment of Colorectal Lung Metastases: Two Centers Retrospective Study
    Myrtle F. Krul, Jan M. van Rees, Amihan M. de Boer, Karlijn K. Neve, Cornelis Verhoef, Koert F.D. Kuhlmann, Tarik R. Baetens, Tineke E. Buffart, Joost L. Knegjens, Houke M. Klomp, Theo J.M. Ruers, Marianne de Vries, Joost Rothbarth, Esther van Meerten, Jo
    Digestive Diseases.2024; 42(6): 538.     CrossRef
  • Clinical outcomes and lung toxicities after lung SABR using dynamic conformal arc therapy: a single-institution cohort study
    Emmanuel Mesny, Myriam Ayadi, Pauline Dupuis, Guillaume Beldjoudi, Ronan Tanguy, Isabelle Martel-Lafay
    Radiation Oncology.2023;[Epub]     CrossRef
  • Knowing When to Use Stereotactic Ablative Radiation Therapy in Oligometastatic Cancer
    Davide Franceschini, Maria Ausilia Teriaca, Luca Dominici, Ciro Franzese, Marta Scorsetti
    Cancer Management and Research.2021; Volume 13: 7009.     CrossRef
  • 12,026 View
  • 174 Download
  • 14 Web of Science
  • 4 Crossref
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