Next Article in Journal
BDNF, Brain, and Regeneration: Insights from Zebrafish
Next Article in Special Issue
Melatonin Sensitizes Human Colorectal Cancer Cells to γ-ray Ionizing Radiation In Vitro and In Vivo
Previous Article in Journal
HPV-18 E6 Oncoprotein and Its Spliced Isoform E6*I Regulate the Wnt/β-Catenin Cell Signaling Pathway through the TCF-4 Transcriptional Factor
Previous Article in Special Issue
Oridonin Enhances Radiation-Induced Cell Death by Promoting DNA Damage in Non-Small Cell Lung Cancer Cells
Article Menu
Issue 10 (October) cover image

Export Article

Open AccessArticle

Relationship between the Regulation of Caspase-8-Mediated Apoptosis and Radioresistance in Human THP-1-Derived Macrophages

Department of Radiation Science, Hirosaki University Graduate School of Health Sciences, 66–1 Hon-cho, Hirosaki, Aomori 036-8564, Japan
Department of Radiological Technology, Hirosaki University School of Health Sciences, 66–1 Hon-cho, Hirosaki, Aomori 036-8564, Japan
Graduate School of Education, Hirosaki University, 1 Bunkyo-cho, Hirosaki, Aomori 036-8560, Japan
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(10), 3154;
Received: 10 August 2018 / Revised: 3 October 2018 / Accepted: 12 October 2018 / Published: 13 October 2018
(This article belongs to the Collection Radiation Toxicity in Cells)
PDF [3415 KB, uploaded 13 October 2018]


Radiosensitivity varies depending on the cell type; highly differentiated cells typically exhibit greater radioresistance. We recently demonstrated that human macrophages derived from THP-1 monocytic cells, which lack TP53, are highly resistant to radiation-induced apoptosis compared with undifferentiated THP-1 cells. However, the mechanisms by which THP-1 cells acquire radioresistance during differentiation remain unknown. Herein, we investigated the mechanisms by which THP-1-derived macrophages develop p53-independent radioresistance by analyzing DNA damage responses and apoptotic pathways. Analysis of γ-H2AX foci, which indicates the formation of DNA double-strand breaks (DSB), suggested that a capacity to repair DSB of macrophages is comparable to that of radiosensitive THP-1 cells. Furthermore, treatment with inhibitors against DSB repair-related proteins failed to enhance radiation-induced apoptosis in THP-1-derrived macrophages. Analysis of the apoptotic pathways showed that radiosensitive THP-1 cells undergo apoptosis through the caspase-8/caspase-3 cascade after irradiation, whereas this was not observed in the macrophages. Caspase-8 protein expression was lower in macrophages than in THP-1 cells, whereas mRNA expressions were comparable between both cell types. Co-treatment with a proteasome inhibitor and ionizing radiation effectively induced apoptosis in macrophages in a caspase-8-dependent manner. Results suggest that the regulation of caspase-8-mediated apoptosis during differentiation plays a role in the p53-independent radioresistance of THP-1-derived macrophages. View Full-Text
Keywords: ionizing radiation; radioresistance; caspase-8; macrophages; apoptosis ionizing radiation; radioresistance; caspase-8; macrophages; apoptosis

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Share & Cite This Article

MDPI and ACS Style

Yoshino, H.; Konno, H.; Ogura, K.; Sato, Y.; Kashiwakura, I. Relationship between the Regulation of Caspase-8-Mediated Apoptosis and Radioresistance in Human THP-1-Derived Macrophages. Int. J. Mol. Sci. 2018, 19, 3154.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top