Selective radiosensitization by nitazoxanide of quiescent clonogenic colon cancer tumour cells

• Published in: Oncology letters 2022-04, Vol.23 (4), p.1, Article 123
• Main Authors: Karlsson, Henning, Fryknas, Marten, Senkowski, Wojciech, Larsson, Rolf, Nygren, Peter
• Format: Article
• Language: English
• Subjects: Animal experimentation; Antiviral drugs; Cancer; Cancer therapies; Care and treatment; Cell culture; Chemotherapy; clonogenic; Colon cancer; Colorectal cancer; Computer software industry; Cytotoxicity; Drug dosages; Experiments; Fluorescence; Hypoxia; nitazoxanide; Proteins; Radiation; Radiation therapy; radiosensitizer; spheroid; Spheroids; Tumors
• ISSN: 1792-1074; 1792-1082; 1792-1082
• DOI: 10.3892/ol.2022.13243

Nitazoxanide is a Food and Drug Administrationapproved antiprotozoal drug recently demonstrated to be selectively active against quiescent and glucose-deprived tumour cells. This drug also has several characteristics that suggest its potential as a radiosensitizer. The present study aimed to investigate the interaction between nitazoxanide and radiation on human colon cancer cells cultured as monolayers, and to mimic key features of solid tumours in patients, as spheroids, as well as in xenografts in mice. In the present study, colon cancer HCT116 green fluorescent protein (GFP) cells were exposed to nitazoxanide, radiation or their combination. Cell survival was analysed by using total cell kill and clonogenic assays. DNA double-strand breaks were evaluated in the spheroid experiments, and HCT116 GFP cell xenograft tumours in mice were used to investigate the effect of nitazoxanide and radiation in vivo. In the clonogenic assay, nitazoxanide synergistically and selectively sensitized cells grown as spheroids to radiation. However, this was not observed in cells cultured as monolayers, as demonstrated in the total cell kill assays, and much less with the clinically established sensitizer 5-fuorouracil. The sensitizing effect from nitazoxanide was confrmed via spheroid [gamma]-H2A histone family member X staining. Nitazoxanide and radiation alone similarly inhibited the growth of HCT116 GFP cell xenograft tumours in mice with no evidence of synergistic interaction. In conclusion, nitazoxanide selectively targeted quiescent glucose-deprived tumour cells and sensitized these cells to radiation in vitro. Nitazoxanide also inhibited tumour growth in vivo. Thus, nitazoxanide is a candidate for repurposing into an anticancer drug, including its use as a radiosensitizer.