www.oncotarget.com Oncotarget, 2020, Vol. 11, (No. 31), pp: 2959-2972 Research Paper Thymoquinone induces apoptosis and DNA damage in 5-Fluorouracil-resistant colorectal cancer stem/progenitor cells Farah Ballout1, Alissar Monzer1, Maamoun Fatfat1, Hala El Ouweini1, Miran A. Jaffa2, Rana Abdel-Samad3, Nadine Darwiche3, Wassim Abou-Kheir4 and Hala Gali-Muhtasib1,4 1Department of Biology, American University of Beirut, Lebanon 2Department of Epidemiology and Population Health, American University of Beirut, Lebanon 3Department of Biochemistry and Molecular Genetics, American University of Beirut, Lebanon 4Center for Drug Discovery and Department of Anatomy, Cell Biology and Physiological Sciences, American University of Beirut, Lebanon Correspondence to: Hala Gali-Muhtasib, email:
[email protected] Wassim Abou-Kheir, email:
[email protected] Keywords: thymoquinone; colorectal cancer stem cells; 5-Fluorouracil resistance; colonospheres; apoptosis Received: October 08, 2019 Accepted: December 16, 2019 Published: August 04, 2020 Copyright: Ballout et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT The high recurrence rates of colorectal cancer have been associated with a small population of cancer stem cells (CSCs) that are resistant to the standard chemotherapeutic drug, 5-fluorouracil (5FU). Thymoquinone (TQ) has shown promising antitumor properties on numerous cancer systems both in vitro and in vivo; however, its effect on colorectal CSCs is poorly established. Here, we investigated TQ’s potential to target CSCs in a three-dimensional (3D) sphere-formation assay enriched for a population of colorectal cancer stem/progenitor cells.