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Disulfiram, a Re-positioned Aldehyde Dehydrogenase Inhibitor, Enhances Radiosensitivity of Human Glioblastoma Cells In Vitro
Hyeon Kang Koh, Soo Yeon Seo, Jin Ho Kim, Hak Jae Kim, Eui Kyu Chie, Seung-Ki Kim, Il Han Kim
Cancer Res Treat. 2019;51(2):696-705.   Published online August 13, 2018
DOI: https://doi.org/10.4143/crt.2018.249
AbstractAbstract PDFPubReaderePub
Purpose
Glioblastoma, the most common brain tumor in adults, has poor prognosis. The purpose of this study was to determine the effect of disulfiram (DSF), an aldehyde dehydrogenase inhibitor, on in vitro radiosensitivity of glioblastoma cells with different methylation status of O6-methylguanine-DNA methyltransferase (MGMT) promoter and the underlying mechanism of such effect.
Materials and Methods
Five human glioblastoma cells (U138MG, T98G, U251MG, U87MG, and U373MG) and one normal human astrocyte (NHA) cell were cultured and treated with DSF or 6MV X-rays (0, 2, 4, 6, and 8 Gy). For combined treatment, cells were treated with DSF before irradiation. Surviving fractions fit from cell survival based on colony forming ability. Apoptosis, DNA damage repair, and cell cycle distributionwere assayed bywestern blot for cleaved caspase-3, γH2AX staining, and flow cytometry, respectively.
Results
DSF induced radiosensitization in most of the glioblastoma cells, especially, in the cells with radioresistance as wildtype unmethylated promoter (MGMT-wt), but did not in normal NHA cell. DSF augmented or induced cleavage of caspase-3 in all cells after irradiation. DSF inhibited repair of radiation-induced DNA damage in MGMT-wt cells, but not in cells with methylated MGMT promoter. DSF abrogated radiation-induced G2/M arrest in T98G and U251MG cells.
Conclusion
Radiosensitivity of glioblastoma cells were preferentially enhanced by pre-irradiation DSF treatment compared to normal cell, especially radioresistant cells such as MGMT-wt cells. Induction of apoptosis or inhibition of DNA damage repair may underlie DSF-induced radiosensitization. Clinical benefit of combining DSF with radiotherapy should be investigated in the future.

Citations

Citations to this article as recorded by  
  • The role of KDM4A‐mediated histone methylation on temozolomide resistance in glioma cells through the HUWE1/ROCK2 axis
    Xi‐Xi Li, Jia‐Kun Xu, Wei‐Jie Su, Hong‐Lin Wu, Kun Zhao, Chang‐Ming Zhang, Xiang‐Kun Chen, Li‐Xuan Yang
    The Kaohsiung Journal of Medical Sciences.2024; 40(2): 161.     CrossRef
  • Glioblastoma Therapy: Past, Present and Future
    Elena Obrador, Paz Moreno-Murciano, María Oriol-Caballo, Rafael López-Blanch, Begoña Pineda, Julia Gutiérrez-Arroyo, Alba Loras, Luis Gonzalez-Bonet, Conrado Martinez-Cadenas, José Estrela, María Marqués-Torrejón
    International Journal of Molecular Sciences.2024; 25(5): 2529.     CrossRef
  • Exploring Disulfiram’s Anticancer Potential: PLGA Nano-Carriers for Prolonged Drug Delivery and Potential Improved Therapeutic Efficacy
    Ibrahim Dumbuya, Ana Maria Pereira, Ibrahim Tolaymat, Adnan Al Dalaty, Basel Arafat, Matt Webster, Barbara Pierscionek, Mouhamad Khoder, Mohammad Najlah
    Nanomaterials.2024; 14(13): 1133.     CrossRef
  • Targeting Retinaldehyde Dehydrogenases to Enhance Temozolomide Therapy in Glioblastoma
    Rafael Jiménez, Andrada Constantinescu, Muhube Yazir, Paula Alfonso-Triguero, Raquel Pequerul, Xavier Parés, Mileidys Pérez-Alea, Ana Paula Candiota, Jaume Farrés, Julia Lorenzo
    International Journal of Molecular Sciences.2024; 25(21): 11512.     CrossRef
  • Clinical, pharmacological, and formulation evaluation of disulfiram in the treatment of glioblastoma - a systematic literature review
    Beáta-Mária Benkő, Dimitrios A. Lamprou, Anna Sebestyén, Romána Zelkó, István Sebe
    Expert Opinion on Drug Delivery.2023; 20(4): 541.     CrossRef
  • Effect of Disulfiram and Copper Plus Chemotherapy vs Chemotherapy Alone on Survival in Patients With Recurrent Glioblastoma
    Katja Werlenius, Sara Kinhult, Tora Skeidsvoll Solheim, Henriette Magelssen, David Löfgren, Munila Mudaisi, Sofia Hylin, Jiri Bartek, Michael Strandéus, Magnus Lindskog, Havyan Bahroz Rashid, Louise Carstam, Sasha Gulati, Ole Solheim, Jiri Bartek, Øyvind
    JAMA Network Open.2023; 6(3): e234149.     CrossRef
  • Disulfiram/Copper induces antitumor activity against gastric cancer via the ROS/MAPK and NPL4 pathways
    Yao Liu, Xin Guan, Meiling Wang, Naixue Wang, Yutong Chen, Baolei Li, Zhuxuan Xu, Fangwei Fu, Cheng Du, Zhendong Zheng
    Bioengineered.2022; 13(3): 6579.     CrossRef
  • Disulfiram in glioma: Literature review of drug repurposing
    Shiyu Zhong, Shengyu Liu, Xin Shi, Xudong Zhang, Kunhang Li, Guojun Liu, Lishuai Li, Shanwei Tao, Bowen Zheng, Weichen Sheng, Ziyin Ye, Qichen Xing, Qingqing Zhai, Lijie Ren, Ying Wu, Yijun Bao
    Frontiers in Pharmacology.2022;[Epub]     CrossRef
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    Hany E. Marei
    Cancer Cell International.2022;[Epub]     CrossRef
  • Formulation Comprising Arsenic Trioxide and Dimercaprol Enhances Radiosensitivity of Pancreatic Cancer Xenografts
    Renyan Tang, Jianmin Zhu, Ying Liu, Ning Wu, Jinbin Han
    Technology in Cancer Research & Treatment.2021;[Epub]     CrossRef
  • Antioxidant and Antiproliferative Activity of Finasteride against Glioblastoma Cells
    Hyeon Ji Kim, Tae-Jun Kim, Yu Gyung Kim, Chaeeun Seong, Jin-Hwa Cho, Wanil Kim, Kyung-Ha Lee, Do-Yeon Kim
    Pharmaceutics.2021; 13(9): 1410.     CrossRef
  • Disulfiram Sensitizes a Therapeutic-Resistant Glioblastoma to the TGF-β Receptor Inhibitor
    Chan-Chuan Liu, Cheng-Lin Wu, Meng-Xuan Lin, Chun-I Sze, Po-Wu Gean
    International Journal of Molecular Sciences.2021; 22(19): 10496.     CrossRef
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    Hong Li, Jingyu Wang, Chunfu Wu, Lihui Wang, Zhe-Sheng Chen, Wei Cui
    Drug Discovery Today.2020; 25(6): 1099.     CrossRef
  • Radiosensitizing high-Z metal nanoparticles for enhanced radiotherapy of glioblastoma multiforme
    Jinyeong Choi, Gaeun Kim, Su Bin Cho, Hyung-Jun Im
    Journal of Nanobiotechnology.2020;[Epub]     CrossRef
  • Disulfiram as a Therapeutic Agent for Metastatic Malignant Melanoma—Old Myth or New Logos?
    Francisco Meraz-Torres, Sarah Plöger, Claus Garbe, Heike Niessner, Tobias Sinnberg
    Cancers.2020; 12(12): 3538.     CrossRef
  • Repurposing Disulfiram as An Anti-Cancer Agent: Updated Review on Literature and Patents
    Elmira Ekinci, Sagar Rohondia, Raheel Khan, Qingping P. Dou
    Recent Patents on Anti-Cancer Drug Discovery.2019; 14(2): 113.     CrossRef
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  • 297 Download
  • 20 Web of Science
  • 17 Crossref
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Effect of Time Interval between Breast-Conserving Surgery and Radiation Therapy on Outcomes of Node-Positive Breast Cancer Patients Treated with Adjuvant Doxorubicin/Cyclophosphamide Followed by Taxane
Hyeon Kang Koh, Kyung Hwan Shin, Kyubo Kim, Eun Sook Lee, In Hae Park, Keun Seok Lee, Jungsil Ro, So-Youn Jung, Seeyoun Lee, Seok Won Kim, Han-Sung Kang, Eui Kyu Chie, Wonshik Han, Dong-Young Noh, Kyung-Hun Lee, Seock-Ah Im, Sung Whan Ha
Cancer Res Treat. 2016;48(2):483-490.   Published online June 5, 2015
DOI: https://doi.org/10.4143/crt.2015.111
AbstractAbstract PDFPubReaderePub
Purpose
This study evaluated the effect of surgery-radiotherapy interval (SRI) on outcomes in patients treated with adjuvant radiotherapy (RT) after breast-conserving surgery (BCS) and adjuvant four cycles of doxorubicin/cyclophosphamide (AC) followed by four cycles of taxane. Materials and Methods From 1999 to 2007, 397 eligible patients were diagnosed. The effect of SRI on outcomes was analyzed using a Cox proportional hazards model, and a maximal chi-square method was used to identify optimal cut-off value of SRI for each outcome.
Results
The median SRI was 6.7 months (range, 5.6 to 10.3 months). A SRI of 7 months was the significant cut-off value for distant metastasis-free survival (DMFS) and disease-free survival (DFS) using a maximal chi-square method. For overall survival, a significant cut-off value was not found. The patients with SRI > 7 months had worse 6-year DMFS and DFS than those with SRI ≤ 7 months on univariate analysis (DMFS, 81% vs. 91%, p=0.003; DFS, 78% vs. 89%, p=0.002). On multivariate analysis, SRI > 7 months did not affect DMFS and DFS. Conclusion RT delayed for more than 7 months after BCS and adjuvant four cycles of AC followed by four cycles of taxane did not compromise clinical outcomes.

Citations

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  • Timing of postmastectomy radiotherapy following adjuvant chemotherapy for high-risk breast cancer: A post hoc analysis of a randomised controlled clinical trial
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    Journal of Racial and Ethnic Health Disparities.2021; 8(1): 147.     CrossRef
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    Marissa C van Maaren, Reini W Bretveld, Jan J Jobsen, Renske K Veenstra, Catharina GM Groothuis-Oudshoorn, Hendrik Struikmans, John H Maduro, Luc JA Strobbe, Philip MP Poortmans, Sabine Siesling
    British Journal of Cancer.2017; 117(2): 179.     CrossRef
  • 11,505 View
  • 126 Download
  • 10 Web of Science
  • 9 Crossref
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