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

Abstract

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.

Inclusion of Nitrofurantoin into the Realm of Cancer Chemotherapy via Biology-Oriented Synthesis and Drug Repurposing

“…Immunostaining and P-ATM shuttling assessment was performed as described previously . Cells were grown on glass coverslips and treated at 50% confluency with the compounds under investigation at the indicated concentration for 4 h. Afterward, media were removed, and cells were washed with PBS.…”

“…Immunostaining and P-ATM shuttling assessment was performed as described previously. 60 Cells were grown on glass coverslips and treated at 50% confluency with the compounds under investigation at the indicated concentration for 4 h. Afterward, media were removed, and cells were washed with PBS. Cells were then fixed with 4% paraformaldehyde (PFA) in PBS for 20 min and permeabilized with 0.5% Triton X-100 in PBS for 30 min at room temperature.…”

The BET Inhibitor JQ1 Potentiates the Anticlonogenic Effect of Radiation in Pancreatic Cancer Cells

“…The plating efficiency (PE) was calculated as: PE = (number of colonies counted)/(number of cells plated). The clonogenic survival fraction (SF) for each treatment was calculated as: SF = [(# of colonies counted)/(# cells plated x PE) x 100] ( 15 , 19 – 21 ). Data are reported as average survival fraction ± SEM.…”

The Role of Thymoquinone in Inflammatory Response in Chronic Diseases

“…CRC is one of three major causes of death worldwide involving energy metabolism disorder in human cells [ 58 ]. One study proposed that TQ can effectively target and eliminate CRC cells, mainly by associating with cell cycle arrest and DNA damage in CRC cells [ 38 , 59 ]. In addition, a combination of TQ with ionizing radiation reduced DNA repair and stemness of CRC [ 38 ].…”

“…One study proposed that TQ can effectively target and eliminate CRC cells, mainly by associating with cell cycle arrest and DNA damage in CRC cells [ 38 , 59 ]. In addition, a combination of TQ with ionizing radiation reduced DNA repair and stemness of CRC [ 38 ]. TQ is an important component in the regulation of metabolism in CRC.…”