Thymoquinone Radiosensitizes Human Colorectal Cancer Cells in 2D and 3D Culture Models

Cancers

Wassim Abou-Kheir¹  Alissar Monzer²  Farah Ballout²  Hala Gali-Muhtasib²  Samar Al Bitar²  Nour Saheb³  Ayman Tawil³  Mariam Kanso⁴  Walid Faraj⁴  Samer Doughan⁴  Maher Hussein⁴  Deborah Mukherji⁵ 

[1] Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut 1107-2020, Lebanon;Department of Biology, American University of Beirut, Beirut 1107-2020, Lebanon;Department of Pathology and Laboratory Medicine, American University of Beirut Medical Center, Beirut 1107-2020, Lebanon;Division of General Surgery, Department of Surgery, American University of Beirut Medical Center, Beirut 1107-2020, Lebanon;Division of Hematology/Oncology, Department of Internal Medicine, Faculty of Medicine, American University of Beirut Medical Center, Beirut 1107-2020, Lebanon;

关键词: colorectal cancer;    cancer stem cells;    patient-derived organoids;    colon spheres;    radiosensitization;    DNA repair;   

DOI  :  10.3390/cancers14061363

来源: DOAJ

【 摘 要 】

Resistance of cancer cells and normal tissue toxicity of ionizing radiation (IR) are known to limit the success of radiotherapy. There is growing interest in using IR with natural compounds to sensitize cancer cells and spare healthy tissues. Thymoquinone (TQ) was shown to radiosensitize several cancers, yet no studies have investigated its radiosensitizing effects on colorectal cancer (CRC). Here, we combined TQ with IR and determined its effects in two-dimensional (2D) and three-dimensional (3D) culture models derived from HCT116 and HT29 CRC cells, and in patient-derived organoids (PDOs). TQ sensitized CRC cells to IR and reduced cell viability and clonogenic survival and was non-toxic to non-tumorigenic intestinal cells. TQ sensitizing effects were associated with G2/M arrest and DNA damage as well as changes in key signaling molecules involved in this process. Combining a low dose of TQ (3 µM) with IR (2 Gy) inhibited sphere formation by 100% at generation 5 and this was associated with inhibition of stemness and DNA repair. These doses also led to ~1.4- to ~3.4-fold decrease in organoid forming ability of PDOs. Our findings show that combining TQ and IR could be a promising therapeutic strategy for eradicating CRC cells.

【 授权许可】

Unknown