Ionizing Radiation Combined with Gold Complex Compounds Causes Apoptosis in Colorectal Cancer Cells by Increasing the Level of Caspase-3

Naoyuki Sano; Hironori Yoshino; Yoshiaki Sato; Hideo Honma; Christopher E J Cordonier; Ikuo Kashiwakura

doi:10.2174/0115665240344867241021043636

Ionizing Radiation Combined with Gold Complex Compounds Causes Apoptosis in Colorectal Cancer Cells by Increasing the Level of Caspase-3

Curr Mol Med. 2025 Jan 6. doi: 10.2174/0115665240344867241021043636. Online ahead of print.

Authors

Naoyuki Sano¹, Hironori Yoshino², Yoshiaki Sato³, Hideo Honma⁴, Christopher E J Cordonier⁴, Ikuo Kashiwakura²

Affiliations

¹ Elm Occupational Health Sciences, LLC, 2-9-12, Shimosone, Kokuraminami, Kitakyushu, Fukuoka 800-0217, Japan.
² Department of Radiation Science, Hirosaki University Graduate School of Health Sciences, 66-1 Hon-cho, Hirosaki, Aomori 036-8564, Japan.
³ Department of Medicine, University of Southern California Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
⁴ Materials and Surface Engineering Research Institute, Kanto Gakuin University, 1162-2, Ogikubo, Odawara, Kanagawa 250-0042, Japan.

PMID: 39779551
DOI: 10.2174/0115665240344867241021043636

Abstract

Background: The anticancer activity and radiosensitizing effect of Auranofin, an an-tirheumatic and an approved gold metallic drug, have been investigated from multiple perspectives. In this study, the action of the new gold complex compound TPN-Au(I)-MM4 was compared with that of auranofin.

Methods: The inhibitory effect of 10 μM and 50 μM concentrations on cell proliferation was investigated using the human colon cancer cell lines HCT116 and SW480. The radiosensitizing effect of HCT116 cells was evaluated by measuring the ability to induce apoptotic cell death. The mechanism of action was qualitatively determined via western blotting analysis of the level of cleaved caspase-3 protein.

Results: Auranofin completely inhibited cell proliferation in both cell lines at both concentrations. In contrast, only 50 μM of TPN-Au(I)-MM4 significantly inhibited the proliferation of SW480 cells, but did not affect the proliferation of HCT116 cells. On the other hand, both compounds effectively increased the apoptotic cell death rate when combined with 4 Gy of X-ray irradiation. This mechanism was caused by a significant increase in the level of caspase-3, which is an apoptosis execution factor, by the combination of these two treatments.

Conclusion: Both compounds promoted the significant expression of caspase-3, an apoptosis execution factor, and exhibited radio-sensitizing effects. In particular, TPNAu( I)-MM4 showed no inhibitory effect on cell proliferation alone, but had a significant radiosensitising effect on HCT116 cells. Therefore, TPN-Au(I)-MM4 has the potential for use as a new radiosensitizer.

Keywords: Auranofin; HCT116 cells; TPN-Au(I)-MM4 (tiopronin monovalent-5-mercapto-1-methyltetrazole monomer); Xirradiation; cleaved caspase-3; pan-caspase inhibitor Z-VAD..